#04 Biochemistry Protein Primary/Secondary Structure Lecture for Kevin Ahern’s BB 450/550


Kevin Ahern: …
have a good weekend? Anybody remember it? Or did it just go [makes swooshing noise] and it was gone, right? You wake up and all of a
sudden the weekend’s gone. I can’t quite get the
volume what I want. Can you hear me up there okay? Okay. I have been pleased. I’ve been talking
with quite a few of you that are working the buffer
problems, and that’s a good sign. In my experience, getting started
early is an important component. And making sure that you understand
those is important as well. They have different
levels of complexity. And I will tell you that,
when you get to the one that has the exceeding
a buffer capacity, I will not expect you
to calculate the pH after you exceed the
buffer’s capacity. That’s been an anxiety
for a few students. I’m not going to do that. The problem is
there mainly for you to recognize when you have
exceeded a buffer’s capacity. So the TA’s are going
through the problems in the recitations and
hopefully that is helpful. Is that helping or not helping? Or what’s your experience? Student: Helping. Student: Helping. Kevin Ahern: Helping? Okay. Good. Not helping? Surely it’s not unanimous. Nobody’s going to say it, right? Okay, good, Alright. What I want to do today is dive
more into protein structure. So I said some things
about amino acids. The TA’s will be going
through some calculation of charge problems for you. And I would also tell
you that there are videos of me solving problems of
protein and amino acid charge that are on the class website. In fact, I will
just show you that, since I’ve had a
couple of questions. The videos for those are
over here on the right side. They’re different from the
videos that are over here. So if you look over here, you’ll see some videos
of me working a bunch of problems on that. Okay. Well, last time I
got started talking about primary
structure of protein. And I will remind you that when
we talk about protein structure, we can think of it as occurring
at four different levels, primary, secondary,
tertiary, and quaternary. And so today I’m going
to talk about primary and I will also
talk about secondary, and I don’t know if I’ll
get into tertiary or not, but if I get through
secondary today I’ll be happy. The primary structure of
a protein is the sequence of amino acids comprising
a protein… the sequence. Now, the sequence is
absolutely essential. As I mentioned last time,
the sequence determines all of the other structures. The primary, that is, the
sequence of the protein, the primary structure, determines what the
secondary structure will be, the tertiary structure will be, and the quaternary
structure will be. So that primary sequence
of a protein is important. When cells have mutation
and that mutation affects a coding for a protein, the mutations that affect the
sequence of the amino acids will be the most important ones and will be the ones that
have the most drastic effects. Okay? So that primary structure
is very, very critical. Now, this shows, on the
screen, a polypeptide. It is, unfortunately,
not the best polypeptide they could have picked. But I guess for our purposes, for what we need at this
point, it’ll work okay. What we see is a polypeptide
that has one, two, three, four, five amino acids in it. And we see the two ends
that I talked about before. You remember that
every polypeptideó by the way, I use
the term polypeptide and protein interchangeably. Technically that’s not right. But it’s a fine
line of distinction and I’m not going to make
that distinction this class. If I say polypeptide or protein, We will use those
terms interchangeably. Now, as I said at the very
end of the lecture last time, there are ends of a protein. There’s an amino end, which always has a
free alpha amino group. We can see this is the
amino end over here because it has a free alpha amino group. And we see this is the
carboxyl group over here because it has a free
alpha carboxyl group. That’s the only
place in a polypeptide where we will see a free alpha
amino and a free alpha carboxyl. And the reason for that is
because the peptide bond, which you see right there, gobbles up a free
carboxyl and a free amino. So every time you
have a peptide bond, we lose a free alpha carboxyl
and a free alpha amino. So we see peptide
bond, peptide bond, peptide bond, peptide bond. Okay? Now, another thing that
we see in this schematic is that this actually is
a nice simplification of the structure of a protein. This is an R group. This is an R group. This is an R group. This is an R group. This is an R group. You notice the pattern,
up, down, up, down, up. So we see alternating
sides of this structure that the R groups are on. Now, that’s not
totally surprising. Some of the R groups
are rather large. Look at the size of
the R group on tyrosine. Look at the size of the
R group on phenylalanine. If we try to put them on the
same side of the polypeptide, they’re bulky, and we’re
going to run into problems with atoms that don’t
want to be close together. We’ve already seen the
energy issue with that. Proteins arrange
themselves by shifting bonds to keep those R groups,
as much as it can, away from each other. So one of the ways it
does it is based on what you see right here on the screen. As I will describe to
you in just a little bit, that orientation gives us
a configuration we refer to as a “trans,” and
I will explain why that’s the case in just a second. The other thing I want
you to notice about this is that these, uh…
I guess I’ve said it. There are peptide bonds
that are joining each of the five amino acids together. Now, there’s a better
schematic that I’ll show you in just a second that
will depict this for you a little bit more clearly. I do want you to notice right
here the alpha carboxyl group… I’m sorry, the
alpha carbon group. The alpha carbon group
right here is the one that has the R group on it, the
R group on it, the R group. So the alpha carbon is
going to turn out to be an interesting carbon in
this overall structure. Schematically, what I
showed you on the last figure is this right here. And I told you in words. There is the first R
group, there’s the second, there’s the third, there’s the
fourth, and there’s the fifth. And the R groups have
arranged themselves so that they’re pointing
away from each other. Peptide bonds are
interesting structures. Peptide bonds are something
that can form what’s called a “resonance structure,” and you
learned in organic chemistry that resonance structures
arise as equivalent electronic configurations for certain atoms. The resonance structure
of a peptide bond, this structure is
essentially equivalent to this structure on the right. Well, this structure on
the right, as we look at it, has a double bond. And what we learned
about organic chemi-, what we learned in organic
chemistry about double bonds is the fact that there are
some specific stereochemical orientations that
can happen with those. Those specific orientations
can create what we think of as cis bonds and what
we think of as trans bonds. So here is an alpha carbon. Here is an alpha carbon. And you will notice
that they are oriented, with respect to the double
bond, in a trans configuration, this one being up,
this one being down. Okay? Now that turns out to be very,
very important for understanding the overall structure
of a protein. So even though that resonance
structure isn’t a double bond all of the time, it
behaves as if it is, almost all of the time. So this cis/trans nature of
these alpha carbons are very, very important for us to
understand protein structure. So I’ll emphasize again that
resonance structure gives rise to what are
cis or transóand, by the way, cis
or trans can exist. What we see when we analyze
the structure of proteins is that the trans is
very strongly favored. If the trans is not
very strongly favored, we can imagine that,
when we have a cis, we would have this
bond going down. And as this bond goes down, the R groups may get
into each other’s face, and that’s exactly what
happens in some cases. So having that structure
as a trans is important. This now shows the peptide
bond, as you see here, the carbon to nitrogen, as
if it were a double bond. Well, what you remember,
again, from organic chemistry, is that that double
bond defines a plane. Double bonds don’t rotate. Double bonds are fixed,
and that forms a plane. The plane of that
double bond is shown, what you see on that
blue in the screen. Okay? Again, we see the alpha carbon
in that trans configuration relative to that double bond. Notice, now, again, the
R group is sticking out. There’s the R
group sticking down. The R groups are oriented away
from each other as much as possible. Okay. Now. This figure shows us what
that structure will look like if we try to put that peptide
bond into a cis configuration. If we try to put it into
a cis configuration, now, here’s our big bulky R group,
here’s our bulky R group. Look. They may run into each other. It’s for this reason that we
see the trans configuration favored something like
99.999% of the time. At least 99.999% of the time,
we see the trans double bond, or the trans configuration
favored, not the cis configuration. We do occasionally see the cis. Now, one of the amino
acids actually favors, at least relatively favors,
the cis configuration. It’s the amino
acid called proline. And when I described the structures
of the amino acids to you, I neglected to
point out something very important about proline. Proline is the only amino
acid whose R group makes a bond with the alpha amino. We can see that right here. Here’s the alpha carbon. Here is the R group coming
off, and we see that the R group makes a bond with
the alpha amino group. Now, the significance of
that is because this is a bond to the alpha amino, there is
less flexibility associated with a proline. Prolines do not have as
much ability to rotate bonds as do the other amino acids. Further, we see proline
has some things hanging off the end of it. Okay? And those things hanging
off of the end of it, in either case, can get in
the way of a trans or a cis. So proline is an oddball,
as far as the amino acids go. And proline has a very
strong effect on the structure of proteins in which it’s found. It’s not uncommon, where we
find a proline in a protein, that we actually see
something called a “bend.” And I’ll explain bends
to you in a little bit. But bends arise because
proline is not very flexible and it has some real
structural limitations, and the rest of the
protein has to go along with whatever proline defines. Now, this favoring the
cis is only relative. The trans for proline is
still strongly favored. Probably 99% are
still in the trans. But about 1% of the time,
it’ll flip into the cis. The other ones won’t have that
happen nearly so frequently. So even though proline is
more relatively favored, it’s still probably 99%
of the time hits the, has a trans
configuration set for it. I’ll have a lot more to say
about proline as we get going further along, talking
about structures of proteins. Questions about that? Student: Kevin? Kevin Ahern: Yeah? Student: So it only favors cis
more than the other amino acids. Kevin Ahern: That’s correct. Student: But it’s
still favored as trans. Kevin Ahern: It’s
still favored as trans. That’s correct. Yes, sir? Student: Could you point
to the alpha carbon group? Kevin Ahern: The alpha carbon
is on this guy, right here. So you see the alpha
carbonóuh, let me seeóyeah, the alpha carbon’s right there. So you see that its R group is
bending back over on this guy. See it? It’s making that bond
with the alpha amino group. That’s the only amino
acid that does that, and that causes a
structural limitation on the overall
protein at that point. Yes, sir? Student: Could you go
back to the web page that showed the amino acids in the sequence of the primary
structure [unintelligible]. Kevin Ahern: Yeah. You’re talking about back here? Student: Yeah. So are all the alpha carbons
in the same configuration in terms of R and S? Kevin Ahern: Are they in the
same configuration with respect to R and S? Student: Yes. Kevin Ahern: Uh, buh, buh, bah… I would have to sit down and do it. I don’t know it off
the top of my head. Yes, Janet? Student: So was this, in trans
proline, it can rotate, so it is rotating for that, but it just
isn’t as flexible around the carbon-nitrogen? Kevin Ahern: It’s not
as flexible around there. So it’s rotating. Remember, we’ve
got a double bond. It can be in the cis or trans. That’s the rotation
that we’re talking about. And so the flexibility
I’m talking about refers to the rest of the molecule. The cis and trans of the peptide
bond are still capable of flipping. And as I will show you in just
a little bit, with proline, what happens is, because that alpha
carbon is in a ring, we don’t have the flexibility of the alpha
carbon bonds to rotate in the same way that we have in
the other amino acids. Okay. Where are we at here? Well, now, after I’ve said something
about thatóI’ve told you that the alpha carbons are very important
for us to understand something about protein structureóit’s
important that now that we think about the alpha carbons
in that overall scheme. Here’s our peptide
bond, right here. The peptide bond is behaving
as if it’s a double bond. There are three bonds that are
of interest to us, however, in a given amino acid. Here’s a bond between the alpha
amine and the alpha carbon. Here’s a bond between the alpha
carbon and the alpha carboxyl. Alright? Only the peptide bond is
capable of being a double bond. These guys are each capable,
they’re perfectly single bonds. And single bonds, you
recall, can rotate. Rotation is very, very important for the overall
structure of a protein, because rotation gives
enormous possible structures that can arise. Alright? Now, I’m going to
introduce a concept that I want you to have a
general understanding of, but I’m not going to go into the
specifics of the actual angles. Somebody’s already asked me, “What’s the zero
point for the angles?” And that’s not really what’s
important for us, okay? Because we have the
ability to rotate across these two double bonds, we could imagine that the
structure of this protein will partly be a function of
how those rotational angles are, in fact, set up. Let’s think about this. This guy, right here,
is part of a plane. Right? We can think about this guy as
being the plane of one peptide bond. Alright? So here’s my peptide
bond on the left. On the right, I’ve got
another peptide bond. It’s also a plane. Okay? Everybody with me? Peptide bond on the left,
peptide bond on the right. Okay. When I put my thumbs together, the place where my thumbs
are make that alpha carbon. When I pull this up, it rings. The alpha carbon’s
in between my thumbs. Alright? Now, what happens is there’s
rotation that’s possible. Those planes themselves can
rotate around that alpha carbon. And now we start
thinking, “Oh, wow. “These rotations can, in
fact, also have limitations “in terms of the things
that are out here.” The things that are out here may
start bumping into each other. So there’s going to be
some limits on the way that this guy can rotate and on
the way that this guy can rotate. Those two bonds are
called phi and psi. And phi and psi, specifically, are rotational angles
around the alpha carbon. Phi is between the alpha
amine and the alpha carbon. Psi is between the alpha
carbon and the alpha carboxyl. Phi and psi. So you’ll hear a lot, when you
talk about protein structure, with respect to what
phi and psi actually are. Everybody understand phi and psi? Now, keep in mind, they
are rotational angles. We’re not talking about
this kind of angle. We’re talking about rotation. Rotational angles have
some very, as we will see, some very strict limits on them because of the spatial considerations
that we talked about before. Those spatial considerations
cause major limits for what things
are actually stable. Now, there’s a famous Indian
scientist named Ramachandran. You don’t need to know the name. But Ramachandran was
very astute in recognizing the importance of these
phi and psi angles, because he recognized that
those were the primary variables in determining certain
structures of proteins. And so he plugged
it into a computer. And he plugs it into
a computer and says, “Here’s the geometry of
the peptide that I’ve got. “Here are these groups that
are floating out here in space. “Where are things going
to be too close together? “Because I know if I
get too close together, “the energy
getsówhoa!óprohibitive.” So he plugs it into a computer and just starts
rotating through space and determining where the
angles are that are stable, that is, that have relatively low
energy, they have plenty of room, and where are the angles
that are very unstable, where they have high
energy and would come apart. So he created something we
call a “Ramachandran plot.” Ramachandran plots plot
the angles of phi and psi. Now, I’m just showing you one. I don’t want you to
panic with this, okay? This is mostly informational. I’m not going to ask you to
interpret a Ramachandran plot. Okay? However, Ramachandran
plots are very interesting, because what we see when we
look at a Ramachandran plot, what you see is exactly that. You see, on the y-axis, psi
through 360 degrees of rotation, from +180 to -180. For our purposes, at the
moment, it doesn’t matter, and, as a matter of fact,
it doesn’t matter at all, for our purposes, where zero is. It’s an arbitrary starting
point for us right now. Similarly, phi, along the
x-axis, goes from -180 to +180. So he asked the computer, “Tell me where the regions are
that will be the most stable, “that will be the lowest energy, “not the most ones
that are inhibitive.” And what he found is that there were two major regions
that were there. One was right here
and one was down here. Okay? No, you’re not going
to memorize those angles or any of that sort of stuff. But this is interesting. A good deal of that
space that was out there, that was possible
for rotational angles, gave rise to structures
that were not very stable. That meant that there was
relatively limited amounts of angles that gave rise to
stable structures, and they seemed to be clustered
pretty much into two regions. We’ll see that those
two regions turn out to be very important
for our understanding of the next level
of protein structure. Everybody with me on this? Questions about
Ramachandran plots? I’m going to say a
little bit more about them in just a little bit, also. That’s what I want to say
about primary structure. And when I’m talking
about Ramachandran plots, as we will see, we’re
starting to talk about the next level of
protein structure. That’s called
secondary structure. Now, secondary structure I’m going to give
you a definition secondary structure is the next
higher level of protein structure, and it arises as a result of
interactions between amino acids that are relatively
close in primary sequence. I’ll repeat that. Secondary structure arises
as a result of interactions between amino acids that are
close in primary sequence. They’re close interactions. We don’t see things very far away interacting in secondary structure. Now, technically,
secondary structure involves a regular
repeating structure, as well. I didn’t include that
in the definition, but technically, it does mean
it’s a regular repeating structure. I’m going to show
you some regular repeating structures
in just a bit. The regular repeating structures
I’m going to show you arise becauseof those limitations that we saw in the Ramachandran plot. Well, let’s think about this. Here is a regular repeating structure
we commonly find in proteins. It’s one of the structures for
which Linus Pauling was recognized, ultimately with a Nobel Prize. It’s called the alpha helix. The alpha helix, as you can see
by the structure on the screen, is a regular repeating structure. It’s a coil that goes on and on. You’ve seen DNA. Everybody’s seen DNA. But DNA is a double helix. This is a single helix. Now, this shows three different
views of an alpha helix. And from this perspective
of the alpha helix, we can see, certainly, here,
the helical nature of it here. It’s not quite so easy to see
the helical nature of it here. But what we see is that
there are some hydrogen bonds. See those green dots right
there, or the green dashes? Those are hydrogen
bonds that are helping to stabilize the secondary
structure, this structure for an alpha helix. Hydrogen bonds are
stabilizing this structure. Very important point,
the most important bonds stabilizing secondary
structure are hydrogen bonds, and they’re happening within a
few amino acids of each other. Now we could go through and
we could do all the business of how many amino
acids they are apart and how many there are
per turn, and so forth, and I don’t think that
really tells us anything that’s important
about the structure. The most important things about
this structure are the regularity, the hydrogen bonds, and the
last thing I’m going to mention, which is this thing, right here. If we notice in that
third panel, in C, we can look sort of down the
barrel of the alpha helix. And when we do, look where
the green groups all arise. How have they been
arranged, guys? Outside the helix. Again, we start coming
back to this important point about bulky molecules
need their space, R groups are oriented in an
alpha helix to the outside. Now, one of the things that
we will see about alpha helices is that they are parts of the
overall structure of proteins. Some proteins have almost
exclusively alpha helix, and that’s all they have. They just go on and on and on,
kind of like the EverReady bunny. Ha-ha. Alright? In other cases, more commonly, we see that they go
on for a ways and then we see another
structure arise, etc. If I have a protein that
really only has alpha helix, I have something called
a “fibrous protein.” A fibrous protein. A fibrous protein
has primary structure, it has secondary structure, but
that’s primarily about all it has. And it goes on and
on and on and on. Example? My hair. Hair, has keratin,
that has a structure that just goes on
and on and on and on. It’s fairly boring,
as proteins go. We’ll see some much more
interesting proteins than that. But fibrous proteins
have that characteristic. Now, this shows you
the orientationóand it’s showing you on that schematic
figure that you saw before where the hydrogen
bonds are located. Notice that this hydrogen bond
that is forming with this amino acid that’s several amino
acids away from it, this hydrogen bond
couldn’t interact like this unless there were a coil. It’s the coil that allows
the hydrogen bonds to form, and, conversely, it’s the
hydrogen bonds that help to stabilize the coil. There’s a carbonyl. There’s a hydrogen. And as we saw on
the very first day, those are really good pairs
for making hydrogen bonds. Here we go back to
our Ramachandran plot. What do we see? There is where the
alpha helix is found. The alpha helix, when we
look at all the alpha helices that are out there, we see
that all the alpha helices map in this region very, very tightly. And there are a
lot of things with very similar angles
to alpha helix, out here, for example, that
have Ramachandran angles very much like it. The alpha helix is in a very, very stable region of
the Ramachandran plot. That’s not surprising,
not surprising, at all. Makes sense? I’m going on and on and on. You guys want a joke? Student: Absolutely. Kevin Ahern: It’s a
little dull in here, right? So this is one of
my favorite jokes. There’s this little
guy, named Artie. And he wants to be a hit man. His dream is that he can go and
he can kill people for a living. Make a lot of money
in this, right? He’s got a career set for him
in the mafia or something, right? He decides to go out and do this. So he figures, “Well, I gotta
get started.” So he goes out. He makes a little note. He tacks it up on the
bulletin boards around town and he tacks it up on the telephone
poles, and so on, and so forth. And it says, “Will
kill someone for cheap.” “Will kill someone for cheap. And so he’s got his thing all up
and this guy calls up and says, “Yeah,” he says, “uh, I’ve got
somebody I want you to kill.” He says, “Oh, yeah?” He says, “Yeah.” He says, “I’d like
you to kill my wife.” And he says, “Okay.” He says, “How do you
want me to kill her?” And he says, “I want
you to strangle her.” No problem. He writes this all down. “Where might I find her?” He says, “Well, as
a matter of fact, she’s at the grocery
store right now.” He says, “Okay.” He says, “Can you
kill her right now?” He said, “Yeah.” And he says, “Well, how
much would you charge?” And Artie says, “Well, you
know, I’m getting started.” He says, “I’ll do it for a buck.” [laughter] That’s how you get
started, folks, you know? He said, “I’ll do it for a buck.” The guy says, “That’s great! Yeah!” So Artie trots off
to the grocery store. He gets out there and he looks, and she’s right there in the
middle of the produce section. He looks around and
there’s nobody there. He goes up and he grabs her
by the throat, strangles her, right there in the
produce section. “Yes! I’m set!” Uh-oh. Somebody saw him. Somebody saw him. Alright? “Damn! This could be serious” He goes, he grabs this
person and he strangles them! You can’t have a witness, right? I mean, if you’re going to get
started, you can’t have witnesses. So he goes and he
strangles this person right there in the grocery store. He’s all “uh-oh.” There’s a third one. He goes over. “My lucky day. This wasn’t the way I envisioned
this thing getting started.” So he goes over, he
grabs this person, he strangles them. He looks around and he goes
racing out of the grocery store. And the police catch him. And the next day, the
headline in the newspaper says, “Artie Chokes Three for a
Dollar at the Grocery Store.” [class laughing and groaning] Oh, that was bad, wasn’t it? Artie chokes three for… [class laughing] I will tell you some
jokes later in the term, and so I want you to remember,
okay, that all I have to do is say, “Artie chokes three for a
dollar at the grocery store,” and you’re going
to laugh at those. You may not laugh at
them, but if you do, then there’s my
punch line that works. Artie chokes. Here’s an alpha helix. Here’s a schematic representation
of the structure of a protein, showing alpha helices. You’ll notice that this
is not a fibrous protein. This is a protein
that has an alpha helix that goes for a little ways and then we have a, um, bend. And then it goes for a ways
and then we have a bend. And then it goes for a ways
and then we have a bend, etc. What we see about the structure
in most proteins is that they have regular repeating structures
for a certain region and then something kind of interferes
with their ability to remain alpha helical in nature. I’ve mentioned one amino acid today
that might interfere with that. What would you
suppose that would be? Students: Proline. Kevin Ahern: Proline! Proline is going to have some
limitations, in terms of angles, and proline may, in fact, interfere
with the regular helical nature that we see here. Now, I’m going to show you an
exception, actually, probably on Wednesday, to that, but proline
is one that can really interfere with a regular
repeating structure. A second structure that is a
repeating structure that is, in fact, a secondary structure,
is known as a beta strand. Let’s, first of all, look
where beta strands appear. Beta strands appear in Ramachandran
plots, as you can see hereóno surpriseóagain, in the most
stable region of a protein. You can see it’s actually a
bigger stable region of the Ramachandran plot. Student: Kevin? Kevin Ahern: Yeah. Student: There’s right-handed
and left-handed alpha… Kevin Ahern: I can’t see you. Where’re you at? Student: … alpha helices, there’s
right-handed and left-handed? Kevin Ahern: Yes. There are right-handed and
left-handed, but right-handed is, by far, the predominant, and,
in fact, some people argue if left-handed even occurs. Student: Okay. Kevin Ahern: Yeah. But right-handed is the
predominant form, yes. Was that the question? Or was there something else? Student: Sometimes I feel like
if you flipped it over it’d be a left-handed one. Kevin Ahern: No. What you’ll see is that the
orientation, actually, if you want to come by my office, I’ll show you
an example of a right-handed versus a left-handed helix. And they do differ. And if you flip it upside down, it
still remains a right-handed helix. It has nothing to do
with the orientation. But come by, I’ll show you, okay? Good question. Beta strands. Beta strandsóthis is a little
harder to see in this imageóI’m going to show you actually
a better image of that. It’s going to look very much like
that first one that I showed you, which was the up, down,
up, down, up, down, right? That very first image, where I
showed you the protein where the R groups were oriented up, down
with respect to each other, is a very good model for
what we call beta strands. And I call them beta strands
because there is a strand. When I put them together in a
bunch of strand, I make something called a “sheet.” People commonly call beta
strands “beta sheets” frequently, because they are
arranged in sheets. Silk, for example, is
composed of beta sheets. Now, look at the orientation
here of the R groups. In this case, they’re going out
of the plane of the board, in. Out, in. That way, versus this way. That way, versus this way. And they’re alternating
as they are set up here. They are arranged so as to, again,
space those groups out so that they’re not causing problems
energetically due to their close interactions with each other. Now, these are what are described
as “antiparallel” and these here are described as “parallel.” For
our purposes, it doesn’t really matter, but if you’re
curious, I will tell you, okay? This would be an
exampleóthis one is parallel. That would mean we’re going from
alpha to carboxyl, and alpha to carboxyl in the same direction. Whereas, if they twist around
like this, they’re what’s called antiparallel. That’s all that that means. And strands can be twisted and
turned, bent as appropriate, to form the structures necessary. Here is an example of a protein
that has beta sheets, and they’re arranged in the form of a barrel. We see barrel structures arising
in proteins to help perform important functions. I’ll talk about a couple
of them later in the term. But these barrels are just like,
literally, like a barrel is. So we see at the nanoscopic
level that structures that we can recognize on a macroscopic
level in the real world. Student: Kevin? Kevin Ahern: Yes. Student: Are there any beta
sheets that have parallel and antiparallel structures? Kevin Ahern: Are there beta
sheets that have parallel and antiparallel? I’m sure there are. I couldn’t name one for you
off the top of my head, but yes. Yes. So they’re not exclusive
to one way or the other. Now, I mentioned
turns earlier today. Turns are very important
because it’s turns that interrupt secondary structure. Turns interrupt
secondary structure. And when we see a turn, there’s a
variety of configurations it could have, but a common form has been
identified that involves, in this case, four different amino acids. There are some
that involve three. There are some that
involve even more. But suffice it to say that this
is a common structure that we see. Not surprisingly, one of these
amino acids is proline, very commonly, proline. Now something that may surprise
you is another one of the amino acids that’s involved in this
structure, commonly, and, again, this is not absolute,
but commonly, is glycine. Glycine is the amino acid
that has the smallest R group. It only has a hydrogen. And you would say, “Well, why would
glycine be involved in a turn?” What do you think? There’s this mumbling. What’s that? Student: Because it’s achiral? Kevin Ahern: Not
because it’s achiral. No. It’s achiral because it
has the small R group. But it’s related to
the small R group. Yeah. Student: Is it because it
has reduced steric hindrance? Kevin Ahern: There’s
reduced steric hindrance. Glycine allows for a
lot more flexibility. Glycine allows for a lot
more things to happen. So it actually is favored,
because we’ve got this limitation over here and we’ve
got flexibility over here. Now, in fact, we may be able to
do something that we couldn’t do otherwise, and glycine
will facilitate that. Again, it’s not absolute. But we do commonly
see that in turns. And I won’t go through that. Now, I mentioned, with respect
to alpha helices, that we see them in what are called
fibrous proteins. We also see them in beta strands. As I said, silk is a protein
that’s comprised of beta sheets. That is a bunch of
strands put together. Silk is also a fibrous protein. Your nails, your fingernails,
are fibrous proteins. So fibrous proteins are comprised,
as I said earlier, of primary structure and secondary structure,
but they have very little tertiary or quaternary structure,
as I will be talking about later. So here is an example
of a fibrous protein. We see that, in this case, we
have helical structures and the helical structures
themselves are intertwined. This gives rise, as we
will see, in some cases, to strength of structures. And I’ll have an example
for you, again, next time. This shows a very interesting
characteristic of protein, or portions of a protein. These can be separate proteins or
these can be portions of the same protein that are
interacting with each other. Now, I’d like you to look
at what’s going on with this. When people first discovered
these structures, they found something very interesting as
they were examining amino acid sequences of proteins. By the way, when we find a new
protein, we always want to determine its amino acid sequence, because,
as we know, the amino acid sequence gives rise
to everything else. And we know the amino acid sequence
long before we know the overall structure of the protein. We can make some predictions, but
our predictions, as I will tell you later, aren’t as good
as we would like them to be. So the first thing they noticed
about this class of proteins when they discovered it was that it
had a very interesting thing in its primary structure. Every seven amino acids
or so, there was a leucine. And that was a little
bit of a puzzle. Why is there every seven
amino acids a leucine? And when they started determining
structures, it all made sense. Leucine is one of the
hydrophobic amino acids. It has a hydrophobic side chain. That hydrophobic side chain, as
you recall, doesn’t like water. When they examined thisóhere’s
one strand, with its every seven amino acids we see a leucine. Here’s another strand, either
part of the same protein or part of another protein, that every seven
amino acids also has a leucine. And look what they are doing. They’re interacting
with each other. They’re getting away from water
by interacting with each other, and they’re forming a structure
that we call a “leucine zipper.” This leucine zipper arises because
of the regular nature of the alpha helix. That regular repeating structure
is placing that leucine at the same place out there in space
every time, allowing those leucines to interact. And so we could imagine that if
we wanted to peel these apart, we would do it just like a zipper. And that peeling apart is going
to be relatively easy to do because these are only hydrophobic
interactions that are actually helping to hold these leucines together. And we’ll talk a little bit
more about that in a bit, okay? So leucine zippers arise because of the regularity
of the alpha helix. Now, the structure that you see
on the screen actually is not a secondary structure. The alpha helix is a secondary
structure, but now we’re starting to see what we refer to as
tertiary or quaternary structure. In this case, if it’s in the same
protein, it’s tertiary structure. And I’m going to show you some
other examples of that in a second. But when we see different regions
of proteins that are not close to each other interacting, we see
what we call tertiary structure. Kevin Ahern: A leucine zipper can
be a part of a tertiary structure, that’s correct. I said I was going to
talk about it next time, but I guess I’ll talk about it today. I told you I had an exception
to the rule about proline forming structures that are
helical in nature. One of the most important fibrous
proteins in nature is the most abundant protein in your body. It’s known as collagen. Collagen is literally the
glue that sticks you together. It holds us together. Without collagen, we
are in trouble, okay? Collagen, to give you an idea,
has a structure that looks something… like… this: coils
of coils, like we saw before. Those coils of coils, when we
analyze the sequence of amino acids comprising them, we discover
something very surprising. Look at this sequence. Look at every place where you
see proline, proline, proline, proline, proline, proline. It’s full of proline! Yeah, we have a regular
repeating structure. You might wonder, “What’s
that H-y-p?”, “Hyp” stands for hydroxyproline. So not only do we have proline,
we have a modified form of proline in here called hydroxyproline,
and this guy is just bursting with this stuff! Yet it forms a regular
repeating structure. How is that possible? Well, the answer is
in red, on the screen. Again, glycine is there. And glycine is giving the space
needed to form this regular repeating structure. Essentially, everywhere we see a
proline, we see a glycine, okay? This is facilitating formation of
that regular repeating structure. So this is one of our exceptions. As I said, proline is not
an absolute thing for a turn. But there’s an interesting story
that goes with this and it’s that story that I’ll
finish with today. Hydroxyproline is a
modified form of proline. When I told you about the 20 amino
acids, I said there were amino acids that got modified after
they were made in a protein, and hydroxyproline is an example
of one of those amino acids. It’s put into the
protein as proline, but then it gets modified chemically. That chemical modification
involves putting a hydroxyl group on it, and that hydroxyl group
ultimately comes from Vitamin C. One of the few reactions where
we actually have a vitamin that’s playing an important role
in a chemical process. Vitamin C is ultimately
the source of this. We make hydroxyproline and one of
the reasons that we have to have hydroxyproline is so we can
make strong collagen, okay? Now, this was discovered partly,
originally, back in the days of the old pirates. The pirates would go out. Big, honking, hairy, stinky,
ugly guys going out conquering the world, killing and robbing and
doing all kinds of nasty things, and they would go out on the
ocean for months at a time and they ate salted meat, because
they did have refrigeration. They didn’t exactly have arugula. They didn’t have
any fruit desserts. They had no source of Vitamin C. And so they’d go out as these
big, hunking, ugly guys, and they’d come back as these
puny little wimps. They’d develop a
condition called scurvy. And that scurvy arises from
Vitamin C, and I’m going to tell you what is involved in scurvy. What’s involved in scurvy? Well, these hydroxyl groups
that we put onto proline are very important. Because it turns out that these
hydroxyl groups are reactive with each other such that, when we
start putting them together, they’ll make bonds with each other. We can actually tie these strands
together with covalent bonds that arise from those hydroxyl
groups on proline. If you ever braid your hair, you’ve
got to tie it off with something on the bottom, right? Otherwise, the braid falls out. These chemical bonds that form
between the hydroxyls are actually linking those strands together and
keeping them from falling apart, and giving strength
to the collagen. As a result of Vitamin C,
you have strong collagen. You don’t fall apart. If you don’t have Vitamin C,
you develop scurvy, you have weak collagen, and,
literally, you fall apart. That’s what happens with them. I was going to sing a song, but
I think we will call it a day and save that for another time. See you guys on Wednesday. How you doing? Student: Are there any other
hydrophobic amino acids that form zippers? Or is it just leucine? Kevin Ahern: Leucine zippers
are the best well-known ones. Student: Okay. Kevin: That’s a good question. [no audio] Kevin: [laughs] I should write
one, I suppose, shouldn’t I? Captioning provided by
Disability Access Services at Oregon State University. [END]

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