So beyond the primary structure which is the sequence of amino acids,
we have secondary, tertiary, and quaternary levels of structure for our proteins.
So again, primary structure is simply the amino acid sequence.
Which amino acid with their distinct side groups is linked to the next amino acid?
One might move up a level of organization in structure of proteins,
we get to secondary structure in which we see two distinct patterns of bonding.
This involves hydrogen bonding between the carboxyl group of one amino acid
and the amino group of another.
In the case of the alpha helix,
these are about four amino acids away from each other
but that hydrogen bonding between those groups allows the formation of this alpha helix.
Another formation that we see commonly in secondary structure are beta pleated sheets.
The amino acids sort of associate and form this step-like structure
and again, the carboxyl groups of one end of an amino acid
and the other end in an antiparallel piece will connect
in order to hold the beta pleated sheets together.
We see these structures repeatedly throughout any protein molecule.
When we move up a level from there, we see tertiary structures.
So we have a long polypeptide chain, single amino acids.
In addition to that, we might have alpha helices or beta pleated sheets
and then, tertiary structure is where we see association
between different side groups, so the R-groups of the amino acids.
The secondary structure was hydrogen bonding between the carboxyl and amino groups.
Here, we’re seeing the R-groups interacting.
So tertiary structure can be formed by a number of different interactions.
First of all, we could have hydrophobic exclusion.
Meaning, hydrophobic meaning that it does not like water.
So in general, when we have proteins in solution
for example, hemoglobin, that wants to hold on to oxygen,
then it will create a hydrophobic region in which we can have oxygen bind, right,
or a specific domain in which that oxygen can bind.
Another thing we might see is interaction of R-groups
where we actually have an ionic bond forming
because one is positively charged and one is negatively charged.
And again, we could also see disulfide bridges.
So we have sulfur involved in those.
Those are some of the most strong bonds that we’ll see in proteins.
So as you can see, the shape of an amino acid chain folding into its protein
is determined by the types of R-groups that we see associated with that central carbon.
Quaternary structure is not exhibited in all proteins.
We definitely see primary, secondary, and tertiary structure in every protein.
However, a quaternary structure involves association of multiple different polypeptide chains.
Hemoglobin is a great example
and we’ll come back and visit hemoglobin throughout the rest of the course,
but it has four subunits.
Two alpha subunits, and two beta subunits.
And those are associated together
and drawn together by charges again with the R-groups.
So when we consider tertiary and quaternary structure,
there are several different repetitive folding patterns that we see or motifs.
It’s very common to see a beta pleated sheets with an alpha helix in the middle
and another series of beta pleated sheets which we call a beta alpha beta motif.
We also might see a helix turn helix motif.
And beta barrels are fairly common as we see in membrane channels.
As you can see these different motifs
probably end up causing different regions of the protein to have different functions.
Those different regions of a protein can be called domains.
So one domain might have a function in binding to a membrane
while another domain has a function in binding to a ligand,
and the other domain may interact with the G protein, for example,
and we’ll explore how those different domains interact once we put together the cells
and get some membrane structures, and talk about cell signaling.
Another thing that helps in folding proteins, sometimes proteins become denatured
and we might need to refold them are the chaperone proteins.
Chaperone proteins themselves are proteins with multiple subunits.
However, they sort of act like a barrel
and the barrel will open up and take in a polypeptide chain that’s been misfolded.
It may require a little bit of ATP to fuel the process, give it energy,
so that this chaperon protein or chaperonin as we call it
can then help the protein refold into its shape and release it back into the environment
that it lives in perhaps, the cell.
And so these chaperone proteins, we don’t understand entirely how they work yet,
but we do know that they exist in helping proteins associate to form their shape.
Because if you didn’t have chaperone proteins,
how would you particularly get one polypeptide chain
to associate this positive group with that negative group.
So we know there are assistants along the way
and this is what we’ve learned about so far.
So when a protein is misfolded, it could become denatured.
Denatured means that it’s no longer functional.
It unfolds, it no longer binds with the particular membrane section that it needs to
or it no longer binds with the ligand that it needs to.
A number of different things can cause this denaturation
and that would include things like changes in homeostasis,
for example, pH change could cause the proteins to unfold.
When we think about polar R-groups,
those polar R-groups are interacting with each other
depending on the acidity or basicity of the environment.
So when we change pH,
sometimes those R-groups are no longer interested in each other at all.
Temperature is another variable that can affect how a protein folds or denatures.
Temperature is a great example when we fry an egg.
The protein is in one form.
When we add heat, the proteins change form and we can generally not reverse frying an egg.
So all these changes or denaturations of protein are generally irreversible
which is where chaperone proteins can come in helpfully in cells.
Another impact is ionic concentration.
If we change the ionic concentration inside a cell,
that could also cause the R-groups of a protein to dissociate
because they’re no longer interested in each other.
If the environment becomes particularly positive inside the cell as in lots of positive ions,
then we’ll see the R-groups dissociate
as we would if it becomes particularly negative.