Conformational stability: Protein folding and denaturation | MCAT | Khan Academy
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Conformational stability: Protein folding and denaturation | MCAT | Khan Academy


Let’s talk about
conformational stability and how this relates to protein
folding and denaturation. So first, let’s review
a couple of terms just to make sure we’re
all on the same page. And first we’ll start out
with the term conformation. And the term
“conformation” just refers to a protein’s folded 3D
structure, or, in other words, the active form of a protein. And next, we can review what
the term “denatured” means when you’re talking
about proteins. And denatured
proteins just refer to proteins that have
become unfolded or inactive. So all conformational stability
is really talking about are the various forces
that help to keep a protein folded
in the right way. And these various forces are
the four different levels of protein structure,
and we can review those briefly right here. So recall that the primary
structure of a protein just refers to that
actual sequence of amino acids in that protein. And this is determined by
a protein’s peptide bonds. And then next, you have
secondary structure, which just refers to the local
substructures in a protein, and they are determined by
backbone interactions held together by hydrogen bonds. Then you have
tertiary structure, which just talks
about the overall 3D structure of a single
protein molecule. And this is described by distant
interactions between groups within a single protein. And these interactions are
stabilized by Van der Waals interactions, hydrophobic
packing, and disulfide bonding in addition to the same
hydrogen bonding that helps to determine
secondary structure. And then quaternary
structure just describes the
different interactions between individual
protein subunits. So you have the
folded-up proteins that then come together
to assemble the completed overall protein. And the interaction of these
different protein subunits are stabilized by the
same kinds of bonds that help to determine
tertiary structure. So all of these levels
of protein structure help to stabilize the
folded-up, active conformation of a protein. So why is it so
important to know about the different levels
of protein structure and how they contribute to
conformational stability? Well, like I said, a
protein is only functional when they are in their
proper conformation and their proper 3D form. And an improperly folded– or
degraded, denatured– protein is inactive. So in addition to the four
levels of protein structure that I just reviewed,
there is also another force that helps
to stabilize a protein’s conformation, and that force
is called the solvation shell. Now, the solvation shell
is just a fancy way of describing the
layer of solvent that is surrounding a protein. So say I have a protein
who has all these exterior residues that are overall
positively charged. And picture this protein
in the watery environment of the interior
one of our cells. Then the solvation shell is
going to be the layer of water right next to this
protein molecule. And remember that water
is a polar molecule. So you have the
electronegative oxygen atom with a predominantly
negative charge leaving a positive charge over
next to the hydrogen atoms. The same is true for each
of these water molecules. So now as you can see, the
electronegative oxygen atoms are stabilizing all of the
positively charged amino acid residues on the exterior
of this protein. So, as you can see, the
conformational stability of a protein depends
not only on all of these interactions
that contribute to primary, secondary, tertiary,
and quaternary structure, but also what sort of
environment that protein is in. And all of these
interactions are very crucial for keeping
a protein folded properly so that it can do its job. Now, what happens
when things go wrong? How does a protein become
unfolded and thus inactive? Well, remember that this
is called denaturation. And this can be done by changing
a lot of different parameters within a protein’s
environment, including changing the
temperature, the pH, adding chemical denaturants,
or even adding enzymes. So let’s start with what
happens if you alter the temperature
around a protein. And we can use the
example of an egg when we put it into a
pot of boiling water, because an egg, especially the
white part, is full of protein. And this pot of boiling
water is representing heat. And remember that heat is
really just a form of energy. So when you heat an
egg, the proteins gain energy and
literally shake apart the bonds between the parts
of the amino acid chains, and this causes the
proteins to unfold. So increased
temperature destroys the secondary, tertiary,
and quaternary structure of a protein. But the primary structure
is still preserved. So the takeaway
point is that when you change the temperature of
a protein by heating it up, you destroy all of the different
levels of protein structure except for the
primary structure. So now let’s say you were
to take an egg and then add vinegar, which is
really just an acid. The acid in the vinegar will
break all the ionic bonds that contribute to tertiary
and quaternary structure. So the takeaway point when
you change the pH surrounding a protein is that you have
disruption of ionic bonds. And if we think about this
a little bit more deeply, it makes sense,
because ionic bonds are dependent upon
the interaction of positive and
negative charges. So when you add either
acid or base, which in the case of an acid
is just like adding a bunch of positive charges,
you disrupt the balance between all of
these interactions between the positive
and negative charges within the protein. So now let’s look at how
chemicals denature proteins. Chemical denaturants often
disrupt the hydrogen bonding within a protein. And remember that
hydrogen bonds contribute to secondary, tertiary, all the
way up to quaternary structure. So all of these levels
of protein structure will be disrupted if you
add a chemical denaturant. So let’s take our same example
of a protein with an egg, and say if you were
21 years older, you got your hands
on some alcohol, and you added this to the egg,
then all the hydrogen bonds would be broken up, leaving you
with just linear polypeptide chains. And then finally, let’s
take our hard boiled egg from the temperature
example and lets eat it. So here’s my beautiful
drawing of a person, representing you, eating
this hard-boiled egg. Once the egg enters
our digestive tract, we have enzymes that break down
the already denatured proteins in the egg even further. They take the linear polypeptide
chain, whose primary structure is still intact, and
they break the bonds between the individual amino
acids, the peptide bonds, so that we can absorb these
amino acids from our intestines into our bloodstream,
and then we can use them as building blocks for
our own protein synthesis. And that’s how enzymes can alter
a protein’s primary structure and thus the protein’s overall
conformational stability. So what did we learn? Well, we learned that the
conformational stability refers to all the forces
that keep a protein properly folded in its active form. And this includes all of the
different levels of protein structure as well as
the solvation shell. And we also learned
that a protein can be denatured into
its inactive form by changing a variety of
factors in its environment, including changing the
temperature, the pH, adding chemicals or enzymes.

About James Carlton

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20 thoughts on “Conformational stability: Protein folding and denaturation | MCAT | Khan Academy

  1. Are there any physical forces that can cause protein denaturization, either by breaking the bonds themselves or damaging the Solvation Shield? For example vigorous shaking of a protein, striking it with various electromatic waves, applying external positive or negative charges etc.

  2. Are there any physical forces that can cause protein denaturization, either by breaking the bonds themselves or damaging the Solvation Shield? For example vigorous shaking of a protein, striking it with various electromatic waves, applying external positive or negative charges etc.

  3. So if I'm younger than 21 years old the H bonds wont break from addition of alcohol? Is this why child labor is illegal?

  4. I dont usually comment on tutorials but WOW!!! You completely answered what I needed to be answered in a simplified way. THANK YOU!!!!

  5. Thank you! I have doubt: is it possible for a protein to be active in its primary structure ( the native state to be just the primary structure)? if so, can you give me an example? Thank you 🙂

  6. I feel like the Ph category is inaccurate. After all cant you have acid or base catalyzed hydrolysis of the peptide bonds, and therefore disrupting the primary structure?

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