Protein Structure and Folding

We all have things that challenge us- and
for me- it is folding. Sheets, towels, shirts- let’s just say I
invest in a lot of anti-wrinkle laundry spray. Amazing invention. My issue with folding extends to paper too. I know foldables in the classroom can be a
powerful way to organize concepts, but for me, it was the actual folding part that I
tended to get stuck on. You may think of folding as a convenience-
of a way to take something and make it more organized or condensed so it doesn’t have
to take up as much space. This is true. But in biology, folding can also have a lot
to do with function. We’ve mentioned how amazing proteins are. They can play so many roles. They can make up channels, be a part of structure,
serve as enzymes for important biological processes, be involved with protecting the
body…just to name a few. We’ve also mentioned that you are making
proteins, all the time, in a process known as protein synthesis. But the conclusion of producing a long chain
of amino acids doesn’t necessarily equal a functional protein. There are modifications to a protein that
often need to happen in order for it to be functional. By modifications, we can mean many things. It might be adding certain chemical groups,
such as phosphorylation—something to definitely explore. But another important event to make a functional
protein is—believe it or not—folding. But before we get into protein folding, let’s
talk about shape and why shape is so important. Shape and function, in biology, frequently
go hand in hand. In our cell signaling video, we mention how
protein receptors and the signal molecules that bind them can fit together so perfectly
to start some type of cellular response. Or in our enzyme video, we talk about how
enzymes—which are frequently proteins—have a very specific shape for the substrates that
they build up or break down. When we talk about the way proteins are folded,
we need to understand the different levels of protein structure because there are different
ways of folding that can happen in the different structural levels. The first level of protein structure is primary
structure. This is the sequence of amino acids that make
up a protein. Amino acids are the monomer—which means
the building block—of a protein. They are held together by peptide bonds. In protein synthesis, amino acids are added
to form a polypeptide chain and proteins are made of 1 or more of these polypeptide chains. Genes, which are made of DNA, determine the
order and number of these amino acids. That sequence is critical to the protein’s
structure and function. In our mutations video, we talk about how
one amino acid can be changed in sickle cell disease. Even a single change of an amino acid has
the potential to affect a protein’s function. We do want to point out- each amino acid has
a carboxyl group, an amino group, and a R group- an R group is also called a side chain. So even though we have them drawn here like
a chain of circles, realize that each of those circles we’re drawing is an amino acid like
this. Next, we move on to secondary structure. Folding is really going to start to happen. In secondary structure, the sequence of amino
acids that we mentioned in primary structure, can fold in different ways. The most common ways are the alpha helix and
the beta pleated sheet and which one of these foldings the protein does depends on the amino
acid arrangement it has. Both of these shapes are due largely in part
to hydrogen bonds. Those hydrogen bonds can occur at specific
areas of the protein’s amino acids. Specifically, these are hydrogen bonds involving
the backbone of the amino acid structure- we’re not focusing on the R groups right
now. On to tertiary structure. This is looking at more folding that occurs
in the 3D shape of a functional protein. And a lot of this is due to something we haven’t
mentioned much…the R groups. Also called side chains. See, the amino group and the carboxyl group
are generally standard parts of an amino acid, although the R group found in amino acids
can vary among different amino acids. That means, the R group can define the amino
acid and can make amino acid behave a certain way. For example, some R groups are hydrophilic. They like water. Some R groups are hydrophobic. They don’t. And remember that proteins contain many amino
acids which can contain different R groups and so different areas of the protein can
therefore be impacted based on those R groups. When protein folding is going on, amino acids
with hydrophilic R groups may hang out on the outside while hydrophobic R groups. Where are they? They may hang out in the inside part of the
protein. The 3D shape is due to other interactions
besides hydrophobic interactions. Ionic bonds, Van der Waals interactions, disulfide
bonds, and hydrogen bonds- all involving the R groups- also influence the folding occurring
in tertiary structure. Something to explore. Now when we’ve been talking about a protein,
we’ve been talking about a polypeptide chain that has been folded into a functional protein. But proteins can be made of 1 or more polypeptide
chains and in quaternary structure—you are looking at a protein consisting of more than
1 polypetide chain. Each of these polypeptide chains can be a
subunit and interactions between them such as hydrogen bonds or disulfide bonds can keep
them together. Going back to the folding, I know what you
might be thinking. Who is doing this folding anyway? Are the proteins just folding themselves? Well, the interactions mentioned like hydrogen
bonds and R group interactions are occurring depending on the protein’s own amino acids. One reason why amino acid sequences are very
important for protein function. But folding is far more complex than that,
and there can be intermediate steps involved when a protein is folding. In fact, there’s a phrase you can search
called the protein-folding problem to learn more about the questions scientists continue
to explore regarding protein folding. Research has shown that proteins often have
help in the folding process. Chaperonins, for example, are proteins that
can help with the folding process. They have almost a barrel shape. Proteins go into them, and the chaperonin
tends to have an environment that is ideal for the proteins’ folding. This can help the protein to be folded correctly
so it’s functional. Just wish I had something like that for my
towels. All of these interactions we mentioned in
primary, secondary, tertiary, and quaternary structure are paramount for a mature protein
to have its correct shape so it can carry out its function. And that’s very relevant! There are many diseases that are related to
protein misfoldings. Check out some of our further reading suggestions
in the description about that. One last thing we haven’t mentioned: each
protein has an ideal environment for functioning which might include a certain temperature
or pH range. If the protein is exposed to something outside
of its ideal temperature or pH range- exposed to high heat for example- you can disrupt
the interactions that we have talked about taking place at the different structural levels. This can denature the protein, which disrupts
its shape. This prevents it from functioning correctly. And depending on what caused it to be denatured,
sometimes you are interfering with many levels of protein structure. Sometimes, it’s just one or two levels. Sometimes denaturing a protein may be reversible. But in many other cases…it’s not. The environment that a protein is in definitely
matters for its functioning. Well, that’s it for the amoeba sisters,
and we remind you to stay curious!

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