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.