Hey guys, it's Professor Dave, I want to tell you about proteins.
So we know about amino acids, and these are the monomers that
will form proteins, which are also known as polypeptides. Proteins are polymers of
amino acids, and they are the most diverse type of biomolecule in your body.
Different kinds of proteins include enzymes that catalyze chemical reactions,
receptors that control signaling in your body,
hemoglobin, which carries oxygen throughout the bloodstream, muscle and
organ tissue, which gives your body structure and mobility, and so many other
things. So how do amino acids polymerize? This happens when amino acids form
peptide bonds with one another, such as the peptide bond between these two
glycine units. Peptide bond formation is an example of a dehydration reaction
because the two hydrogens and the oxygen marked in blue are lost, and two
hydrogens plus one oxygen equals a water molecule, so as a water molecule is lost
these two amino acids come together to form a peptide bond, which results in an
amide. An amide is a functional group with a nitrogen atom next to a carbonyl
and this is the functional group that will connect each amino acid during
polymerization. If two amino acids combine we get a dipeptide. If between
three and ten come together, we would call that an oligopeptide, since oligo
means just a few. And if more than ten come together we will call that a
polypeptide, since poly means many and proteins are large polypeptides of
around three hundred to a thousand amino acids that are folded in such a way that
they have some biological activity. When we look at any peptide, we must notice
that there is an N-terminus, meaning the side of the chain that ends with the
amino group, and a C-terminus, the side that ends with the carboxyl group.
By convention we typically write proteins with the N-terminus on the
left and the C-terminus on the right. Each monomeric unit in the polypeptide
is called a residue, so on this structure we should be able to differentiate
between each individual residue and locate the peptide bonds that connect them.
Proteins are very large compared to simple molecules. They contain hundreds
of amino acid residues and they have very specific shapes from which their
function is derived, so let's learn about protein structure.
Protein structure follows a specific hierarchy so let's start first with primary protein structure.
The primary structure of a protein is simply the sequence of amino
acids with no attention paid to any aspect of three-dimensional shape.
We can abbreviate each amino acid residue with either a three-letter code or a one
letter code depending on how much you feel like writing, and here are both sets
of abbreviations for your reference. The shape the protein will take depends on
the primary structure because it is the identity of all the side chains and the
sequence they are found in that determines how a protein will fold up.
To see this in action let's look at secondary protein structure.
Secondary protein structure describes localized conformations of the polypeptide
backbone, meaning the folding pattern that a protein will exhibit over a few
dozen amino acid residues. There are a few different motifs that a protein can
utilize so let's see what those are.
First let's understand that the backbone itself is essentially planar. The peptide
bond has some pi bond character due to resonance, since there is a resonance
structure where the lone pair on the nitrogen forms a pi bond, pushing the pi
bond in the carbonyl up to the oxygen atom. We know that rotation is restricted
around pi bonds so even though it's not a formal pi bond between the carbon and
the nitrogen, the backbone is fairly rigid, while the sigma bonds to the
R groups can freely rotate, so it is mainly the side chains on each residue that
have a flexible conformation.
We also know that molecules with dipoles or formal charges will
attempt to store energy by making electrostatic interactions, and amino
acids have such features. So if this backbone can fold in such a way so as to
let each residue interact with other residues, it will do so, in order to adopt
the lowest-energy conformation. One way it can do this is by forming something
called a beta-pleated sheet. The backbone will extend one way and then turn back
to line up alongside the first part of the chain so that NH bonds from one
section can form dipole-dipole interactions with the carbonyls of an
adjacent section. This stores energy so it is an example of a favorable
conformation and one type of secondary protein structure. Another type of
structural motif is called the alpha helix. This is when the backbone forms a
spiral shape with about three or four amino acids per turn, and all the
R groups pointing out. Here each amide group will interact with the amide group
three residues above and the one three residues below. So beta-pleated sheets and alpha
helices are the most common types of secondary structure, though there are all
kinds of other coils and loops that are a bit more difficult to describe. The key
thing to understand is that at this level the polypeptide backbone begins to
form shapes entirely dependent on how it can best store energy in dipole-dipole
interactions, by adopting the lowest-energy conformation, and these
structures contain so many individual atoms that we begin to depict them as
colored strips rather than with conventional molecular line notation for
practical purposes.
Now let's move on to tertiary protein structure. Tertiary protein structure
involves the further folding of the polypeptide chain to produce its overall
three-dimensional structure. This folding is not random,
it is specific to the protein and will occur in that specific way every time
that particular protein is formed, since it is this shape that gives the protein
its function.
There are a few factors that influence tertiary structure. First, residues with
hydrophobic side chains, like alkyl groups, tend to be found in the interior
of the protein, so that they are not in contact with aqueous solvent. At the same
time, residues with hydrophilic side chains, ones with formal charges or
dipoles on them, tend to be found on the surface of a protein so that they can
make dipole-dipole or ion-dipole interactions with water molecules.
All of this is just a way for the protein to maximize the electrostatic interactions
it can make in solution, which is a big factor in determining the way the protein will fold.
Another motif that stabilizes tertiary structure is
something called a disulfide bond. We know that cysteine has an SH group
called a thiol on its side chain, which is the sulfur analog of a hydroxyl group.
If one cysteine is near another, these thiol groups can react with one another by
mild oxidation to create a disulfide which causes a covalent linkage between
the two sulfur atoms, and therefore can also covalently link two residues
anywhere in the protein. This can help maintain the structural integrity of the
protein through covalent bonds that are much stronger than the dipole-dipole
interactions found in the various secondary structures. Overall, if the
protein is highly folded and compact we would call it a globular protein, whereas
if it is long and spindly we would call it a fibrous protein. Lastly, we can
examine quaternary structure. Some proteins are just one continuous
polypeptide chain, but some proteins involve multiple polypeptide subunits
that can come together to form a larger protein. These units are not covalently
bound, they make only electrostatic interactions with one another, but the
interactions are strong enough to allow the subunits to arrange themselves in
specific ways, and it is the arrangement of these subunits that determines the
quaternary structure of a protein, like hemoglobin, which consists of four
totally separate polypeptides arranged in a
specific way. If a protein is comprised of just one polypeptide then it will not
have quaternary structure. So to summarize, primary structure is just the
sequence of amino acids. Secondary structure is the way the chain begins to
fold on the localized level. Tertiary structure is the complete folding
pattern of an entire polypeptide, and quaternary structure is the way multiple
polypeptide subunits come together to form a larger protein. It is important to
understand that even a tiny change in primary structure can completely change
the overall protein. For example, sickle cell disease is a genetic disorder where
just one amino acid residue in one of the subunits of hemoglobin is changed
from glutamic acid to valine. Because the side chains of those two amino acids are
so different,
the mutation changes the folding pattern at that location, and the resulting
hemoglobin protein, which is responsible for carrying oxygen through the
bloodstream, takes on a different shape, causing the red blood cells that contain
hemoglobin to look like tiny sickles, which can then clog blood vessels.
So we can already begin to see why understanding the structure and function
of biomolecules is crucial if we want to understand health and disease.
Let's keep learning about different biomolecules.
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