2026 New exam review Upload |MCB 150 lecture 1-8 University of Illinois,
Urbana Champaign
Is secondary structure important?
Well, there's the question.
I'm going to give you a couple of examples that I think demonstrate that the answer is a
resounding yes.
The first one is hair.
The primary polypeptide component of hair is a protein called keratin.
Keratin is very rich in alpha helix.
It's almost all alpha helix.
And those keratin proteins are wrapped around each other to make a structure that we call hair.
Now hair is sort of semi-elastic, isn't it?
You can pull on hair and it's got some give to it.
Why?
Because those alpha helices that hold the keratin coil together are stabilized by hydrogen
bonds.
And just a little bit of force or a little bit of heat makes those hydrogen bonds go away.
So you can stretch or heat up hair and it will elongate because you're breaking those hydrogen
bonds.
This is an example from sort of macroscopic on the right to microscopic on the left view.
What we're talking about down here at the bottom is there's our keratin proteins.
They're coiled coils because each one of these coils is itself a long stretch of alpha helix.
So we're talking about lots and lots of hydrogen bonding.
Now this hydrogen bonding can be intentionally destabilized.
You can use heat to get rid of hydrogen bonds.
They're not very strong.
So if you use a curling iron, what does a curling iron do?
It heats up your hair, disrupts those hydrogen bonds, lets the hair stretch out.
You get to form it in whatever new form you want, whatever new shape you want.
And then when you let go and it cools back down, it holds that shape for a while.
It's also possible, that's just heat, and as soon as it cools down, it kind of already starts going
back to the way it was before.
If you go to a salon, instead of just using heat, you can use chemicals to make those new forms
more permanent.
That's what a perm is.
It's chemical reformation of the bonds that hold the keratin together.
But even a perm isn't really permanent, is it?
Eventually, your hair is going to go back to the way your genetics say it wants it to be.
And so if you want the fabulous curls, you've got to get another perm.
So that's one example of the importance of secondary structure.
Here's another one.
This one's a little less well-known, but perhaps more biologically relevant.
Here's polypeptide A and polypeptide B. As you notice, the one on the left, polypeptide A,
happens to be mostly alpha helix.
The one on the right looks like it's about half alpha helix and half beta sheet.
,It should surprise you to learn that polypeptides A and B have the exact same primary
sequence.
Exact same primary sequence.
Now, think about chemistry labs and so forth.
If you have identical reactants,
under identical conditions, you shouldn't expect them to behave differently, right?
Well, biology is no different.
If you've got identical molecules or identical organisms or whatever, if they're the same and
you're treating them the same, you should expect them to behave the same.
That should be your expectation.
So why can I have a single primary sequence that can adopt wildly different secondary
structures?
Because one of them went wrong.
And that's bad enough.
But what's even worse is that the one that misfolded talks the other ones into also misfolding
and becomes a huge problem.
So this is called a prion protein.
Prion protein is naturally occurring in most mammals.
It has a job.
We're not going to talk about what its regular job is, but it's found mostly in your central nervous
system, a lot of it in your brain, and organs that are sort of ancillary to the central nervous
system.
So the regular prion protein has been there the whole time.
It's doing its job, and it looks like the one on the left.
Then you are introduced to the version on the right, the misfolded version of this prion protein,
and it somehow, and since the late 1980s, we've been trying to answer this question and still
don't have an answer that many decades later, how is the one on the right talking the one on the
left into folding the way it's folded?
It's infectious.
In fact, prion is something of a shorthand for proteinaceous infectious particle.
It's not a virus, it's not a bacterium, it's a protein.
It's the only known example of a protein influencing other proteins in this way.
It talks the regularly folded version into folding in the misfolded way.
And notice that in the misfolded version, the one on the right, it's got those beta sheets in it.
Those beta sheets have hydrophobic amino acids exposed to the outside now.
They didn't want to be exposed to the outside, so the proteins, the misfolded versions, start to
stick together.
And when the misfolded versions stick together, they come out of solution, they create these
plaques, and they cause a family of disorders called spongiform encephalopathies.
That's a big phrase.
Anytime you see big, long words like that, try to see if there are elements of those words that
you can tease out and identify.
Pathy, patho, pathic, that means disease or disorder, right?
Cephalo means head, and the prefix en, en, means inside or within.
,So if cephalo means head, then encephalo means brain, the thing inside the head.
So an encephalopathy is a disease of the brain.
All of those parts of the word help it make sense, help identify what it is.
A spongiform encephalopathy is a description of what that brain tissue looks like.
If you do an autopsy on an organism, an individual that has succumbed to one of these
disorders, it looks like a sponge.
It's got holes in it.
This is obviously fatal, and it's a pretty big deal.
And it can happen in a lot of different mammals.
It's most commonly talked about as mad cow disease.
Mad cow disease is the cow, the bovine equivalent or version of a spongiform encephalopathy.
But it isn't limited to cows.
It was first discovered in sheep.
Ranchers were noticing that every once in a while one of their sheep started going crazy, right?
And what they meant by that was they were using their hooves and scraping off their own hair
and skin.
Obviously they were not normal and they died as a result and they would notice that as soon as
one of them had it, pretty soon other ones would come up with it too.
So they called it scrapies.
They had no idea.
They were ranchers.
They're not molecular biologists.
They didn't know what was going on.
They just noticed that their sheep were scraping themselves to death.
It can also be found in deer and elk.
It's called chronic wasting disease in those organisms.
And here's the bad news for the people sitting in this room, it can also be found in humans.
If it's found in humans, there's two different spongiform encephalopathies.
One of them is called Kreutzfeldt-Jakob disease, and the other one is called Kuru.
And it's generally a result of eating brain tissue from an infected disease.
Cow, for example.
This is why when a cow in a herd is found to have mad cow disease, they have to destroy the
whole herd because there's no guarantee that other cows in the herd haven't been affected and
they don't want those cattle going to market with the misfolded prion protein and infecting
humans.
It's fatal.
I know we've been working on this for decades.
We still don't have a cure.
We still don't even know why it's really happening, much less find a cure for it.
The best we can do is prevention and treatment of symptoms.
There is no cure for this.
I think that's a resounding yes to the question, is secondary structure important, right?
So that's secondary structure.
, Remember, secondary structure is stabilized by alpha helices and beta sheets that are held
together by hydrogen bonding between one peptide linkage and another peptide linkage.
Yes, please.
We know a little bit about how it gets through the animal.
It gets out of the brain and into it.
There's prion protein in other tissues.
Sometimes it's in kidneys.
Sometimes it's in liver.
Prion protein is a widespread protein in its normal state.
there's an ability to get wherever else in the body you happen to go, and that's how it can
spread.
That's also why eating kind of any organ meat, it doesn't have to just be brain from an infected
individual like a cow or another human.
There are some cannibalistic, ritualistic,
tribes that feel like they gain power from their ancestors by eating the brains of their recently
deceased.
That's how kuru spreads in a tribe, because if that person happened to die from this disease,
then anybody who eats that tissue is likely to die as well, because they've introduced the
misfolded version into their bodies, which is now one at a time, and it's exponential, right?
One prion protein talks this prion into folding the wrong way.
Now you got two of them.
Then they each go out and do one.
Now you got four.
Then eight.
Then 16.
We're talking about exponential growth of the misfolded version of that protein.
So yes, secondary structure is very important.
Now we move on to the next level of organization.
We call this tertiary structure.
This is the final three-dimensional conformation, where conformation is the fancy biology word
that means shape, the three-dimensional shape.
It's conformation of a given polypeptide.
Remember, there is a difference.
subtle but present between polypeptide and protein.
Some proteins are only functional when you have multiple parts bonded together and working
as a team.
Other proteins are functional as single polypeptides that have folded the right way.
So for some functional proteins, this is the end of the line.
If you are not what we would call a subunit in a multi-subunit protein, that's how we would
describe you if you were one of a number of parts working together.
We would call you subunits in a multi-subunit or multimeric protein.
If you are functional just by yourself, then tertiary structure is the end of the line for you.
Tertiary structure is the answer to the question, what are the forces that are holding that protein
into this shape and not allowing it to go into this shape or this shape or some other shape?
Urbana Champaign
Is secondary structure important?
Well, there's the question.
I'm going to give you a couple of examples that I think demonstrate that the answer is a
resounding yes.
The first one is hair.
The primary polypeptide component of hair is a protein called keratin.
Keratin is very rich in alpha helix.
It's almost all alpha helix.
And those keratin proteins are wrapped around each other to make a structure that we call hair.
Now hair is sort of semi-elastic, isn't it?
You can pull on hair and it's got some give to it.
Why?
Because those alpha helices that hold the keratin coil together are stabilized by hydrogen
bonds.
And just a little bit of force or a little bit of heat makes those hydrogen bonds go away.
So you can stretch or heat up hair and it will elongate because you're breaking those hydrogen
bonds.
This is an example from sort of macroscopic on the right to microscopic on the left view.
What we're talking about down here at the bottom is there's our keratin proteins.
They're coiled coils because each one of these coils is itself a long stretch of alpha helix.
So we're talking about lots and lots of hydrogen bonding.
Now this hydrogen bonding can be intentionally destabilized.
You can use heat to get rid of hydrogen bonds.
They're not very strong.
So if you use a curling iron, what does a curling iron do?
It heats up your hair, disrupts those hydrogen bonds, lets the hair stretch out.
You get to form it in whatever new form you want, whatever new shape you want.
And then when you let go and it cools back down, it holds that shape for a while.
It's also possible, that's just heat, and as soon as it cools down, it kind of already starts going
back to the way it was before.
If you go to a salon, instead of just using heat, you can use chemicals to make those new forms
more permanent.
That's what a perm is.
It's chemical reformation of the bonds that hold the keratin together.
But even a perm isn't really permanent, is it?
Eventually, your hair is going to go back to the way your genetics say it wants it to be.
And so if you want the fabulous curls, you've got to get another perm.
So that's one example of the importance of secondary structure.
Here's another one.
This one's a little less well-known, but perhaps more biologically relevant.
Here's polypeptide A and polypeptide B. As you notice, the one on the left, polypeptide A,
happens to be mostly alpha helix.
The one on the right looks like it's about half alpha helix and half beta sheet.
,It should surprise you to learn that polypeptides A and B have the exact same primary
sequence.
Exact same primary sequence.
Now, think about chemistry labs and so forth.
If you have identical reactants,
under identical conditions, you shouldn't expect them to behave differently, right?
Well, biology is no different.
If you've got identical molecules or identical organisms or whatever, if they're the same and
you're treating them the same, you should expect them to behave the same.
That should be your expectation.
So why can I have a single primary sequence that can adopt wildly different secondary
structures?
Because one of them went wrong.
And that's bad enough.
But what's even worse is that the one that misfolded talks the other ones into also misfolding
and becomes a huge problem.
So this is called a prion protein.
Prion protein is naturally occurring in most mammals.
It has a job.
We're not going to talk about what its regular job is, but it's found mostly in your central nervous
system, a lot of it in your brain, and organs that are sort of ancillary to the central nervous
system.
So the regular prion protein has been there the whole time.
It's doing its job, and it looks like the one on the left.
Then you are introduced to the version on the right, the misfolded version of this prion protein,
and it somehow, and since the late 1980s, we've been trying to answer this question and still
don't have an answer that many decades later, how is the one on the right talking the one on the
left into folding the way it's folded?
It's infectious.
In fact, prion is something of a shorthand for proteinaceous infectious particle.
It's not a virus, it's not a bacterium, it's a protein.
It's the only known example of a protein influencing other proteins in this way.
It talks the regularly folded version into folding in the misfolded way.
And notice that in the misfolded version, the one on the right, it's got those beta sheets in it.
Those beta sheets have hydrophobic amino acids exposed to the outside now.
They didn't want to be exposed to the outside, so the proteins, the misfolded versions, start to
stick together.
And when the misfolded versions stick together, they come out of solution, they create these
plaques, and they cause a family of disorders called spongiform encephalopathies.
That's a big phrase.
Anytime you see big, long words like that, try to see if there are elements of those words that
you can tease out and identify.
Pathy, patho, pathic, that means disease or disorder, right?
Cephalo means head, and the prefix en, en, means inside or within.
,So if cephalo means head, then encephalo means brain, the thing inside the head.
So an encephalopathy is a disease of the brain.
All of those parts of the word help it make sense, help identify what it is.
A spongiform encephalopathy is a description of what that brain tissue looks like.
If you do an autopsy on an organism, an individual that has succumbed to one of these
disorders, it looks like a sponge.
It's got holes in it.
This is obviously fatal, and it's a pretty big deal.
And it can happen in a lot of different mammals.
It's most commonly talked about as mad cow disease.
Mad cow disease is the cow, the bovine equivalent or version of a spongiform encephalopathy.
But it isn't limited to cows.
It was first discovered in sheep.
Ranchers were noticing that every once in a while one of their sheep started going crazy, right?
And what they meant by that was they were using their hooves and scraping off their own hair
and skin.
Obviously they were not normal and they died as a result and they would notice that as soon as
one of them had it, pretty soon other ones would come up with it too.
So they called it scrapies.
They had no idea.
They were ranchers.
They're not molecular biologists.
They didn't know what was going on.
They just noticed that their sheep were scraping themselves to death.
It can also be found in deer and elk.
It's called chronic wasting disease in those organisms.
And here's the bad news for the people sitting in this room, it can also be found in humans.
If it's found in humans, there's two different spongiform encephalopathies.
One of them is called Kreutzfeldt-Jakob disease, and the other one is called Kuru.
And it's generally a result of eating brain tissue from an infected disease.
Cow, for example.
This is why when a cow in a herd is found to have mad cow disease, they have to destroy the
whole herd because there's no guarantee that other cows in the herd haven't been affected and
they don't want those cattle going to market with the misfolded prion protein and infecting
humans.
It's fatal.
I know we've been working on this for decades.
We still don't have a cure.
We still don't even know why it's really happening, much less find a cure for it.
The best we can do is prevention and treatment of symptoms.
There is no cure for this.
I think that's a resounding yes to the question, is secondary structure important, right?
So that's secondary structure.
, Remember, secondary structure is stabilized by alpha helices and beta sheets that are held
together by hydrogen bonding between one peptide linkage and another peptide linkage.
Yes, please.
We know a little bit about how it gets through the animal.
It gets out of the brain and into it.
There's prion protein in other tissues.
Sometimes it's in kidneys.
Sometimes it's in liver.
Prion protein is a widespread protein in its normal state.
there's an ability to get wherever else in the body you happen to go, and that's how it can
spread.
That's also why eating kind of any organ meat, it doesn't have to just be brain from an infected
individual like a cow or another human.
There are some cannibalistic, ritualistic,
tribes that feel like they gain power from their ancestors by eating the brains of their recently
deceased.
That's how kuru spreads in a tribe, because if that person happened to die from this disease,
then anybody who eats that tissue is likely to die as well, because they've introduced the
misfolded version into their bodies, which is now one at a time, and it's exponential, right?
One prion protein talks this prion into folding the wrong way.
Now you got two of them.
Then they each go out and do one.
Now you got four.
Then eight.
Then 16.
We're talking about exponential growth of the misfolded version of that protein.
So yes, secondary structure is very important.
Now we move on to the next level of organization.
We call this tertiary structure.
This is the final three-dimensional conformation, where conformation is the fancy biology word
that means shape, the three-dimensional shape.
It's conformation of a given polypeptide.
Remember, there is a difference.
subtle but present between polypeptide and protein.
Some proteins are only functional when you have multiple parts bonded together and working
as a team.
Other proteins are functional as single polypeptides that have folded the right way.
So for some functional proteins, this is the end of the line.
If you are not what we would call a subunit in a multi-subunit protein, that's how we would
describe you if you were one of a number of parts working together.
We would call you subunits in a multi-subunit or multimeric protein.
If you are functional just by yourself, then tertiary structure is the end of the line for you.
Tertiary structure is the answer to the question, what are the forces that are holding that protein
into this shape and not allowing it to go into this shape or this shape or some other shape?
