Protein Structure

Protein Structure


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. Thanks for watching, guys. Subscribe to my channel for
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