#04 Biochemistry Protein Primary/Secondary Structure Lecture for Kevin Ahern's BB 450/550

Uploaded by oharow on 03.10.2011

Kevin Ahern: ... have a good weekend?
Anybody remember it?
Or did it just go
[makes swooshing noise]
and it was gone, right?
You wake up and all of a sudden the weekend's gone.
I can't quite get the volume what I want.
Can you hear me up there okay?
I have been pleased.
I've been talking with quite a few of you
that are working the buffer problems, and that's a good sign.
In my experience, getting started early is an important component.
And making sure that you understand those is important as well.
They have different levels of complexity.
And I will tell you that, when you get to the one that
has the exceeding a buffer capacity,
I will not expect you to calculate the pH
after you exceed the buffer's capacity.
That's been an anxiety for a few students.
I'm not going to do that.
The problem is there mainly for you
to recognize when you have exceeded a buffer's capacity.
So the TA's are going through the problems
in the recitations and hopefully that is helpful.
Is that helping or not helping?
Or what's your experience?
Student: Helping.
Student: Helping.
Kevin Ahern: Helping?
Not helping?
Surely it's not unanimous.
Nobody's going to say it, right?
Okay, good, Alright.
What I want to do today is dive more into protein structure.
So I said some things about amino acids.
The TA's will be going through some calculation
of charge problems for you.
And I would also tell you that there are videos
of me solving problems of protein and amino acid charge
that are on the class website.
In fact, I will just show you that,
since I've had a couple of questions.
The videos for those are over here on the right side.
They're different from the videos that are over here.
So if you look over here,
you'll see some videos of me working a bunch
of problems on that.
Well, last time I got started talking
about primary structure of protein.
And I will remind you that when we talk about protein structure,
we can think of it as occurring at four different levels,
primary, secondary, tertiary, and quaternary.
And so today I'm going to talk about primary
and I will also talk about secondary,
and I don't know if I'll get into tertiary or not,
but if I get through secondary today I'll be happy.
The primary structure of a protein is the sequence
of amino acids comprising a protein... the sequence.
Now, the sequence is absolutely essential.
As I mentioned last time, the sequence determines
all of the other structures.
The primary, that is, the sequence of the protein,
the primary structure,
determines what the secondary structure will be,
the tertiary structure will be,
and the quaternary structure will be.
So that primary sequence of a protein is important.
When cells have mutation and that mutation affects
a coding for a protein,
the mutations that affect the sequence of the amino acids
will be the most important ones
and will be the ones that have the most drastic effects.
So that primary structure is very, very critical.
Now, this shows, on the screen, a polypeptide.
It is, unfortunately, not the best polypeptide
they could have picked.
But I guess for our purposes,
for what we need at this point, it'll work okay.
What we see is a polypeptide that has one, two, three,
four, five amino acids in it.
And we see the two ends that I talked about before.
You remember that every polypeptideó
by the way, I use the term polypeptide
and protein interchangeably.
Technically that's not right.
But it's a fine line of distinction
and I'm not going to make that distinction this class.
If I say polypeptide or protein,
We will use those terms interchangeably.
Now, as I said at the very end of the lecture last time,
there are ends of a protein.
There's an amino end,
which always has a free alpha amino group.
We can see this is the amino end over here because
it has a free alpha amino group.
And we see this is the carboxyl group over here
because it has a free alpha carboxyl group.
That's the only place in a polypeptide
where we will see a free alpha amino and a free alpha carboxyl.
And the reason for that is because the peptide bond,
which you see right there,
gobbles up a free carboxyl and a free amino.
So every time you have a peptide bond,
we lose a free alpha carboxyl and a free alpha amino.
So we see peptide bond, peptide bond,
peptide bond, peptide bond.
Now, another thing that we see in this schematic is
that this actually is a nice simplification
of the structure of a protein.
This is an R group.
This is an R group.
This is an R group.
This is an R group.
This is an R group.
You notice the pattern, up, down, up, down, up.
So we see alternating sides of this structure
that the R groups are on.
Now, that's not totally surprising.
Some of the R groups are rather large.
Look at the size of the R group on tyrosine.
Look at the size of the R group on phenylalanine.
If we try to put them on the same side of the polypeptide,
they're bulky, and we're going to run into problems
with atoms that don't want to be close together.
We've already seen the energy issue with that.
Proteins arrange themselves by shifting bonds
to keep those R groups, as much as it can,
away from each other.
So one of the ways it does it is based on what
you see right here on the screen.
As I will describe to you in just a little bit,
that orientation gives us a configuration we refer
to as a "trans," and I will explain why
that's the case in just a second.
The other thing I want you to notice about
this is that these, uh... I guess I've said it.
There are peptide bonds that are joining each
of the five amino acids together.
Now, there's a better schematic that I'll show you
in just a second that will depict this for you
a little bit more clearly.
I do want you to notice right here the alpha carboxyl group...
I'm sorry, the alpha carbon group.
The alpha carbon group right here is the one that
has the R group on it, the R group on it, the R group.
So the alpha carbon is going to turn out to be an
interesting carbon in this overall structure.
Schematically, what I showed you on the last figure
is this right here.
And I told you in words.
There is the first R group, there's the second,
there's the third, there's the fourth, and there's the fifth.
And the R groups have arranged themselves so that
they're pointing away from each other.
Peptide bonds are interesting structures.
Peptide bonds are something that can form what's called a
"resonance structure," and you learned in organic chemistry
that resonance structures arise as equivalent electronic
configurations for certain atoms.
The resonance structure of a peptide bond,
this structure is essentially equivalent
to this structure on the right.
Well, this structure on the right, as we look at it,
has a double bond.
And what we learned about organic chemi-,
what we learned in organic chemistry about double bonds
is the fact that there are some specific stereochemical
orientations that can happen with those.
Those specific orientations can create what we think
of as cis bonds and what we think of as trans bonds.
So here is an alpha carbon.
Here is an alpha carbon.
And you will notice that they are oriented,
with respect to the double bond, in a trans configuration,
this one being up, this one being down.
Now that turns out to be very, very important for understanding
the overall structure of a protein.
So even though that resonance structure isn't a double bond
all of the time, it behaves as if it is,
almost all of the time.
So this cis/trans nature of these alpha carbons are very,
very important for us to understand protein structure.
So I'll emphasize again that resonance structure gives
rise to what are cis or transóand,
by the way, cis or trans can exist.
What we see when we analyze the structure of proteins
is that the trans is very strongly favored.
If the trans is not very strongly favored,
we can imagine that, when we have a cis,
we would have this bond going down.
And as this bond goes down,
the R groups may get into each other's face,
and that's exactly what happens in some cases.
So having that structure as a trans is important.
This now shows the peptide bond, as you see here,
the carbon to nitrogen, as if it were a double bond.
Well, what you remember, again, from organic chemistry,
is that that double bond defines a plane.
Double bonds don't rotate.
Double bonds are fixed, and that forms a plane.
The plane of that double bond is shown,
what you see on that blue in the screen.
Again, we see the alpha carbon in that trans configuration
relative to that double bond.
Notice, now, again, the R group is sticking out.
There's the R group sticking down.
The R groups are oriented away from each other as much as possible.
This figure shows us what that structure will look like
if we try to put that peptide bond into a cis configuration.
If we try to put it into a cis configuration, now,
here's our big bulky R group, here's our bulky R group.
They may run into each other.
It's for this reason that we see the trans configuration
favored something like 99.999% of the time.
At least 99.999% of the time, we see the trans double bond,
or the trans configuration favored, not the cis configuration.
We do occasionally see the cis.
Now, one of the amino acids actually favors,
at least relatively favors, the cis configuration.
It's the amino acid called proline.
And when I described the structures of the amino acids to you,
I neglected to point out something
very important about proline.
Proline is the only amino acid whose R group makes a bond
with the alpha amino.
We can see that right here.
Here's the alpha carbon.
Here is the R group coming off, and we see that the R group
makes a bond with the alpha amino group.
Now, the significance of that is because this is a bond
to the alpha amino, there is less flexibility associated
with a proline.
Prolines do not have as much ability to rotate bonds
as do the other amino acids.
Further, we see proline has some things hanging off
the end of it.
And those things hanging off of the end of it,
in either case, can get in the way of a trans or a cis.
So proline is an oddball, as far as the amino acids go.
And proline has a very strong effect on the structure
of proteins in which it's found.
It's not uncommon, where we find a proline in a protein,
that we actually see something called a "bend."
And I'll explain bends to you in a little bit.
But bends arise because proline is not very flexible
and it has some real structural limitations,
and the rest of the protein has to go along
with whatever proline defines.
Now, this favoring the cis is only relative.
The trans for proline is still strongly favored.
Probably 99% are still in the trans.
But about 1% of the time, it'll flip into the cis.
The other ones won't have that happen nearly so frequently.
So even though proline is more relatively favored,
it's still probably 99% of the time hits the,
has a trans configuration set for it.
I'll have a lot more to say about proline as we get going
further along, talking about structures of proteins.
Questions about that?
Student: Kevin?
Kevin Ahern: Yeah?
Student: So it only favors cis more than the other amino acids.
Kevin Ahern: That's correct.
Student: But it's still favored as trans.
Kevin Ahern: It's still favored as trans.
That's correct.
Yes, sir?
Student: Could you point to the alpha carbon group?
Kevin Ahern: The alpha carbon is on this guy, right here.
So you see the alpha carbonóuh, let me seeóyeah,
the alpha carbon's right there.
So you see that its R group is bending back over on this guy.
See it?
It's making that bond with the alpha amino group.
That's the only amino acid that does that,
and that causes a structural limitation
on the overall protein at that point.
Yes, sir?
Student: Could you go back to the web page
that showed the amino acids
in the sequence of the primary structure [unintelligible].
Kevin Ahern: Yeah.
You're talking about back here?
Student: Yeah.
So are all the alpha carbons in the same configuration
in terms of R and S?
Kevin Ahern: Are they in the same configuration with respect to
R and S?
Student: Yes.
Kevin Ahern: Uh, buh, buh, bah...
I would have to sit down and do it.
I don't know it off the top of my head.
Yes, Janet?
Student: So was this, in trans proline, it can rotate, so it is
rotating for that, but it just isn't as flexible around the
Kevin Ahern: It's not as flexible around there.
So it's rotating.
Remember, we've got a double bond.
It can be in the cis or trans.
That's the rotation that we're talking about.
And so the flexibility I'm talking about refers to
the rest of the molecule.
The cis and trans of the peptide bond are still capable of flipping.
And as I will show you in just a little bit, with proline, what
happens is, because that alpha carbon is in a ring, we don't have
the flexibility of the alpha carbon bonds to rotate in the same
way that we have in the other amino acids.
Where are we at here?
Well, now, after I've said something about thatóI've told you that
the alpha carbons are very important for us to understand something
about protein structureóit's important that now that we think
about the alpha carbons in that overall scheme.
Here's our peptide bond, right here.
The peptide bond is behaving as if it's a double bond.
There are three bonds that are of interest to us, however,
in a given amino acid.
Here's a bond between the alpha amine and the alpha carbon.
Here's a bond between the alpha carbon and the alpha carboxyl.
Only the peptide bond is capable of being a double bond.
These guys are each capable, they're perfectly single bonds.
And single bonds, you recall, can rotate.
Rotation is very, very important
for the overall structure of a protein,
because rotation gives enormous possible structures
that can arise.
Now, I'm going to introduce a concept
that I want you to have a general understanding of,
but I'm not going to go into the specifics of the actual angles.
Somebody's already asked me,
"What's the zero point for the angles?"
And that's not really what's important for us, okay?
Because we have the ability to rotate across
these two double bonds,
we could imagine that the structure of this protein
will partly be a function of how those rotational angles are,
in fact, set up.
Let's think about this.
This guy, right here, is part of a plane.
We can think about this guy as being the plane of one peptide bond.
So here's my peptide bond on the left.
On the right, I've got another peptide bond.
It's also a plane.
Everybody with me?
Peptide bond on the left, peptide bond on the right.
When I put my thumbs together,
the place where my thumbs are make that alpha carbon.
When I pull this up, it rings.
The alpha carbon's in between my thumbs.
Now, what happens is there's rotation that's possible.
Those planes themselves can rotate around that alpha carbon.
And now we start thinking, "Oh, wow.
"These rotations can, in fact, also have limitations
"in terms of the things that are out here."
The things that are out here may start bumping into each other.
So there's going to be some limits on the way
that this guy can rotate and on the way that this guy can rotate.
Those two bonds are called phi and psi.
And phi and psi, specifically,
are rotational angles around the alpha carbon.
Phi is between the alpha amine and the alpha carbon.
Psi is between the alpha carbon and the alpha carboxyl.
Phi and psi.
So you'll hear a lot, when you talk about protein structure,
with respect to what phi and psi actually are.
Everybody understand phi and psi?
Now, keep in mind, they are rotational angles.
We're not talking about this kind of angle.
We're talking about rotation.
Rotational angles have some very, as we will see,
some very strict limits on them
because of the spatial considerations that we talked about before.
Those spatial considerations cause major limits
for what things are actually stable.
Now, there's a famous Indian scientist named Ramachandran.
You don't need to know the name.
But Ramachandran was very astute in recognizing
the importance of these phi and psi angles,
because he recognized that those were the primary variables
in determining certain structures of proteins.
And so he plugged it into a computer.
And he plugs it into a computer and says,
"Here's the geometry of the peptide that I've got.
"Here are these groups that are floating out here in space.
"Where are things going to be too close together?
"Because I know if I get too close together,
"the energy getsówhoa!óprohibitive."
So he plugs it into a computer
and just starts rotating through space
and determining where the angles are that are stable,
that is, that have relatively low energy, they have plenty of room,
and where are the angles that are very unstable,
where they have high energy and would come apart.
So he created something we call a "Ramachandran plot."
Ramachandran plots plot the angles of phi and psi.
Now, I'm just showing you one.
I don't want you to panic with this, okay?
This is mostly informational.
I'm not going to ask you to interpret a Ramachandran plot.
However, Ramachandran plots are very interesting,
because what we see when we look at a Ramachandran plot,
what you see is exactly that.
You see, on the y-axis, psi through 360 degrees of rotation,
from +180 to -180.
For our purposes, at the moment, it doesn't matter,
and, as a matter of fact, it doesn't matter at all,
for our purposes, where zero is.
It's an arbitrary starting point for us right now.
Similarly, phi, along the x-axis, goes from -180 to +180.
So he asked the computer,
"Tell me where the regions are that will be the most stable,
"that will be the lowest energy,
"not the most ones that are inhibitive."
And what he found is that there
were two major regions that were there.
One was right here and one was down here.
No, you're not going to memorize those angles
or any of that sort of stuff.
But this is interesting.
A good deal of that space that was out there,
that was possible for rotational angles,
gave rise to structures that were not very stable.
That meant that there was relatively limited amounts of angles
that gave rise to stable structures,
and they seemed to be clustered pretty much into two regions.
We'll see that those two regions turn out
to be very important for our understanding
of the next level of protein structure.
Everybody with me on this?
Questions about Ramachandran plots?
I'm going to say a little bit more about them
in just a little bit, also.
That's what I want to say about primary structure.
And when I'm talking about Ramachandran plots,
as we will see, we're starting to talk about
the next level of protein structure.
That's called secondary structure.
Now, secondary structure
I'm going to give you a definition
secondary structure is the next higher level of protein structure,
and it arises as a result of interactions between amino acids
that are relatively close in primary sequence.
I'll repeat that.
Secondary structure arises as a result of interactions
between amino acids that are close in primary sequence.
They're close interactions.
We don't see things very far away
interacting in secondary structure.
Now, technically, secondary structure
involves a regular repeating structure, as well.
I didn't include that in the definition,
but technically, it does mean it's a regular repeating structure.
I'm going to show you some regular
repeating structures in just a bit.
The regular repeating structures I'm going to show you arise
becauseof those limitations that
we saw in the Ramachandran plot.
Well, let's think about this.
Here is a regular repeating structure we commonly find in proteins.
It's one of the structures for which Linus Pauling was recognized,
ultimately with a Nobel Prize.
It's called the alpha helix.
The alpha helix, as you can see by the structure on the screen,
is a regular repeating structure.
It's a coil that goes on and on.
You've seen DNA.
Everybody's seen DNA.
But DNA is a double helix.
This is a single helix.
Now, this shows three different views of an alpha helix.
And from this perspective of the alpha helix,
we can see, certainly, here, the helical nature of it here.
It's not quite so easy to see the helical nature of it here.
But what we see is that there are some hydrogen bonds.
See those green dots right there, or the green dashes?
Those are hydrogen bonds that are helping
to stabilize the secondary structure, this structure
for an alpha helix.
Hydrogen bonds are stabilizing this structure.
Very important point, the most important bonds
stabilizing secondary structure are hydrogen bonds,
and they're happening within a few amino acids of each other.
Now we could go through and we could do all the business
of how many amino acids they are apart
and how many there are per turn, and so forth,
and I don't think that really tells us anything
that's important about the structure.
The most important things about this structure are the regularity,
the hydrogen bonds, and the last thing I'm going to mention,
which is this thing, right here.
If we notice in that third panel, in C,
we can look sort of down the barrel of the alpha helix.
And when we do, look where the green groups all arise.
How have they been arranged, guys?
Outside the helix.
Again, we start coming back to this important point
about bulky molecules need their space,
R groups are oriented in an alpha helix to the outside.
Now, one of the things that we will see about alpha helices
is that they are parts of the overall structure of proteins.
Some proteins have almost exclusively alpha helix,
and that's all they have.
They just go on and on and on, kind of like the EverReady bunny.
In other cases, more commonly,
we see that they go on for a ways and then
we see another structure arise, etc.
If I have a protein that really only has alpha helix,
I have something called a "fibrous protein."
A fibrous protein.
A fibrous protein has primary structure,
it has secondary structure, but that's primarily about all it has.
And it goes on and on and on and on.
My hair.
Hair, has keratin, that has a structure
that just goes on and on and on and on.
It's fairly boring, as proteins go.
We'll see some much more interesting proteins than that.
But fibrous proteins have that characteristic.
Now, this shows you the orientationóand
it's showing you on that schematic figure that you saw before
where the hydrogen bonds are located.
Notice that this hydrogen bond that is forming with this amino acid
that's several amino acids away from it,
this hydrogen bond couldn't interact like this
unless there were a coil.
It's the coil that allows the hydrogen bonds to form,
and, conversely, it's the hydrogen bonds that help
to stabilize the coil.
There's a carbonyl.
There's a hydrogen.
And as we saw on the very first day,
those are really good pairs for making hydrogen bonds.
Here we go back to our Ramachandran plot.
What do we see?
There is where the alpha helix is found.
The alpha helix, when we look at all the alpha helices
that are out there, we see that all the alpha helices
map in this region very,
very tightly.
And there are a lot of things with
very similar angles to alpha helix,
out here, for example, that have Ramachandran angles
very much like it.
The alpha helix is in a very,
very stable region of the Ramachandran plot.
That's not surprising, not surprising, at all.
Makes sense?
I'm going on and on and on.
You guys want a joke?
Student: Absolutely.
Kevin Ahern: It's a little dull in here, right?
So this is one of my favorite jokes.
There's this little guy, named Artie.
And he wants to be a hit man.
His dream is that he can go and he can kill people for a living.
Make a lot of money in this, right?
He's got a career set for him in the mafia or something, right?
He decides to go out and do this.
So he figures, "Well, I gotta get started." So he goes out.
He makes a little note.
He tacks it up on the bulletin boards around town
and he tacks it up on the telephone poles, and so on, and so forth.
And it says, "Will kill someone for cheap."
"Will kill someone for cheap.
And so he's got his thing all up and this guy calls up and says,
"Yeah," he says, "uh, I've got somebody I want you to kill."
He says, "Oh, yeah?"
He says, "Yeah."
He says, "I'd like you to kill my wife."
And he says, "Okay."
He says, "How do you want me to kill her?"
And he says, "I want you to strangle her."
No problem.
He writes this all down.
"Where might I find her?"
He says, "Well, as a matter of fact,
she's at the grocery store right now."
He says, "Okay."
He says, "Can you kill her right now?"
He said, "Yeah."
And he says, "Well, how much would you charge?"
And Artie says, "Well, you know, I'm getting started."
He says, "I'll do it for a buck."
That's how you get started, folks, you know?
He said, "I'll do it for a buck."
The guy says, "That's great!
So Artie trots off to the grocery store.
He gets out there and he looks,
and she's right there in the middle of the produce section.
He looks around and there's nobody there.
He goes up and he grabs her by the throat, strangles her,
right there in the produce section.
I'm set!"
Somebody saw him.
Somebody saw him.
This could be serious"
He goes, he grabs this person and he strangles them!
You can't have a witness, right?
I mean, if you're going to get started, you can't have witnesses.
So he goes and he strangles this person
right there in the grocery store.
He's all "uh-oh."
There's a third one.
He goes over.
"My lucky day.
This wasn't the way I envisioned this thing getting started."
So he goes over, he grabs this person,
he strangles them.
He looks around and he goes racing out of the grocery store.
And the police catch him.
And the next day, the headline in the newspaper says,
"Artie Chokes Three for a Dollar at the Grocery Store."
[class laughing and groaning]
Oh, that was bad, wasn't it?
Artie chokes three for...
[class laughing]
I will tell you some jokes later in the term,
and so I want you to remember, okay, that all I have to do is say,
"Artie chokes three for a dollar at the grocery store,"
and you're going to laugh at those.
You may not laugh at them, but if you do,
then there's my punch line that works.
Artie chokes.
Here's an alpha helix.
Here's a schematic representation of the structure of a protein,
showing alpha helices.
You'll notice that this is not a fibrous protein.
This is a protein that has an alpha helix
that goes for a little ways
and then we have a, um, bend.
And then it goes for a ways and then we have a bend.
And then it goes for a ways and then we have a bend, etc.
What we see about the structure in most proteins is that they have
regular repeating structures for a certain region and then
something kind of interferes with their ability to remain alpha
helical in nature.
I've mentioned one amino acid today that might interfere with that.
What would you suppose that would be?
Students: Proline.
Kevin Ahern: Proline!
Proline is going to have some limitations, in terms of angles, and
proline may, in fact, interfere with the regular helical nature
that we see here.
Now, I'm going to show you an exception, actually, probably on
Wednesday, to that, but proline is one that can really interfere
with a regular repeating structure.
A second structure that is a repeating structure that is, in fact,
a secondary structure, is known as a beta strand.
Let's, first of all, look where beta strands appear.
Beta strands appear in Ramachandran plots, as you can see hereóno
surpriseóagain, in the most stable region of a protein.
You can see it's actually a bigger stable region of the
Ramachandran plot.
Student: Kevin?
Kevin Ahern: Yeah.
Student: There's right-handed and left-handed alpha...
Kevin Ahern: I can't see you.
Where're you at?
Student: ... alpha helices, there's right-handed and left-handed?
Kevin Ahern: Yes.
There are right-handed and left-handed, but right-handed is, by
far, the predominant, and, in fact, some people argue if
left-handed even occurs.
Student: Okay.
Kevin Ahern: Yeah.
But right-handed is the predominant form, yes.
Was that the question?
Or was there something else?
Student: Sometimes I feel like if you flipped it over it'd be a
left-handed one.
Kevin Ahern: No.
What you'll see is that the orientation, actually, if you want to
come by my office, I'll show you an example of a right-handed versus
a left-handed helix.
And they do differ.
And if you flip it upside down, it still remains a right-handed helix.
It has nothing to do with the orientation.
But come by, I'll show you, okay?
Good question.
Beta strands.
Beta strandsóthis is a little harder to see in this imageóI'm going
to show you actually a better image of that.
It's going to look very much like that first one that I showed you,
which was the up, down, up, down, up, down, right?
That very first image, where I showed you the protein where the
R groups were oriented up, down with respect to each other,
is a very good model for what we call beta strands.
And I call them beta strands because there is a strand.
When I put them together in a bunch of strand, I make something
called a "sheet."
People commonly call beta strands "beta sheets" frequently,
because they are arranged in sheets.
Silk, for example, is composed of beta sheets.
Now, look at the orientation here of the R groups.
In this case, they're going out of the plane of the board, in.
Out, in.
That way, versus this way.
That way, versus this way.
And they're alternating as they are set up here.
They are arranged so as to, again, space those groups out so that
they're not causing problems energetically due to their close
interactions with each other.
Now, these are what are described as "antiparallel" and these here
are described as "parallel." For our purposes, it doesn't really
matter, but if you're curious, I will tell you, okay?
This would be an exampleóthis one is parallel.
That would mean we're going from alpha to carboxyl, and alpha to
carboxyl in the same direction.
Whereas, if they twist around like this,
they're what's called antiparallel.
That's all that that means.
And strands can be twisted and turned, bent as appropriate, to form
the structures necessary.
Here is an example of a protein that has beta sheets, and they're
arranged in the form of a barrel.
We see barrel structures arising in proteins to help perform
important functions.
I'll talk about a couple of them later in the term.
But these barrels are just like, literally, like a barrel is.
So we see at the nanoscopic level that structures that we can
recognize on a macroscopic level in the real world.
Student: Kevin?
Kevin Ahern: Yes.
Student: Are there any beta sheets that have parallel and
antiparallel structures?
Kevin Ahern: Are there beta sheets that have parallel and
I'm sure there are.
I couldn't name one for you off the top of my head, but yes.
So they're not exclusive to one way or the other.
Now, I mentioned turns earlier today.
Turns are very important because it's turns that interrupt
secondary structure.
Turns interrupt secondary structure.
And when we see a turn, there's a variety of configurations it could
have, but a common form has been identified that involves, in this
case, four different amino acids.
There are some that involve three.
There are some that involve even more.
But suffice it to say that this is a common structure that we see.
Not surprisingly, one of these amino acids is proline, very
commonly, proline.
Now something that may surprise you is another one of the amino
acids that's involved in this structure, commonly, and, again,
this is not absolute, but commonly, is glycine.
Glycine is the amino acid that has the smallest R group.
It only has a hydrogen.
And you would say, "Well, why would glycine be involved in a turn?"
What do you think?
There's this mumbling.
What's that?
Student: Because it's achiral?
Kevin Ahern: Not because it's achiral.
It's achiral because it has the small R group.
But it's related to the small R group.
Student: Is it because it has reduced steric hindrance?
Kevin Ahern: There's reduced steric hindrance.
Glycine allows for a lot more flexibility.
Glycine allows for a lot more things to happen.
So it actually is favored, because we've got this
limitation over here and we've got flexibility over here.
Now, in fact, we may be able to do something that we couldn't do
otherwise, and glycine will facilitate that.
Again, it's not absolute.
But we do commonly see that in turns.
And I won't go through that.
Now, I mentioned, with respect to alpha helices, that we see them
in what are called fibrous proteins.
We also see them in beta strands.
As I said, silk is a protein that's comprised of beta sheets.
That is a bunch of strands put together.
Silk is also a fibrous protein.
Your nails, your fingernails, are fibrous proteins.
So fibrous proteins are comprised, as I said earlier, of primary
structure and secondary structure, but they have very little
tertiary or quaternary structure, as I will be talking about later.
So here is an example of a fibrous protein.
We see that, in this case, we have helical structures and the
helical structures themselves are intertwined.
This gives rise, as we will see, in some cases,
to strength of structures.
And I'll have an example for you, again, next time.
This shows a very interesting characteristic of protein, or
portions of a protein.
These can be separate proteins or these can be portions of the same
protein that are interacting with each other.
Now, I'd like you to look at what's going on with this.
When people first discovered these structures, they found
something very interesting as they were examining amino acid
sequences of proteins.
By the way, when we find a new protein, we always want to determine
its amino acid sequence, because, as we know, the amino acid
sequence gives rise to everything else.
And we know the amino acid sequence long before we know the overall
structure of the protein.
We can make some predictions, but our predictions, as I will tell
you later, aren't as good as we would like them to be.
So the first thing they noticed about this class of proteins when
they discovered it was that it had a very interesting thing in its
primary structure.
Every seven amino acids or so, there was a leucine.
And that was a little bit of a puzzle.
Why is there every seven amino acids a leucine?
And when they started determining structures, it all made sense.
Leucine is one of the hydrophobic amino acids.
It has a hydrophobic side chain.
That hydrophobic side chain, as you recall, doesn't like water.
When they examined thisóhere's one strand, with its every seven
amino acids we see a leucine.
Here's another strand, either part of the same protein or part of
another protein, that every seven amino acids also has a leucine.
And look what they are doing.
They're interacting with each other.
They're getting away from water by interacting with each other,
and they're forming a structure that we call a "leucine zipper."
This leucine zipper arises because of the regular nature of the
alpha helix.
That regular repeating structure is placing that leucine at the
same place out there in space every time,
allowing those leucines to interact.
And so we could imagine that if we wanted to peel these apart,
we would do it just like a zipper.
And that peeling apart is going to be relatively easy to do because
these are only hydrophobic interactions that are actually helping
to hold these leucines together.
And we'll talk a little bit more about that in a bit, okay?
So leucine zippers arise because
of the regularity of the alpha helix.
Now, the structure that you see on the screen actually is not
a secondary structure.
The alpha helix is a secondary structure, but now we're starting
to see what we refer to as tertiary or quaternary structure.
In this case, if it's in the same protein, it's tertiary structure.
And I'm going to show you some other examples of that in a second.
But when we see different regions of proteins that are not close
to each other interacting, we see what we call tertiary structure.
Kevin Ahern: A leucine zipper can be a part of a tertiary structure,
that's correct.
I said I was going to talk about it next time,
but I guess I'll talk about it today.
I told you I had an exception to the rule about proline forming
structures that are helical in nature.
One of the most important fibrous proteins in nature is the most
abundant protein in your body.
It's known as collagen.
Collagen is literally the glue that sticks you together.
It holds us together.
Without collagen, we are in trouble, okay?
Collagen, to give you an idea, has a structure that looks
something... like... this: coils of coils, like we saw before.
Those coils of coils, when we analyze the sequence of amino acids
comprising them, we discover something very surprising.
Look at this sequence.
Look at every place where you see proline, proline, proline,
proline, proline, proline.
It's full of proline!
Yeah, we have a regular repeating structure.
You might wonder, "What's that H-y-p?", "Hyp" stands for
So not only do we have proline, we have a modified form of proline
in here called hydroxyproline, and this guy
is just bursting with this stuff!
Yet it forms a regular repeating structure.
How is that possible?
Well, the answer is in red, on the screen.
Again, glycine is there.
And glycine is giving the space needed to form this regular
repeating structure.
Essentially, everywhere we see a proline, we see a glycine, okay?
This is facilitating formation of that regular repeating structure.
So this is one of our exceptions.
As I said, proline is not an absolute thing for a turn.
But there's an interesting story that goes with this and it's that
story that I'll finish with today.
Hydroxyproline is a modified form of proline.
When I told you about the 20 amino acids, I said there were amino
acids that got modified after they were made in a protein, and
hydroxyproline is an example of one of those amino acids.
It's put into the protein as proline,
but then it gets modified chemically.
That chemical modification involves putting a hydroxyl group on
it, and that hydroxyl group ultimately comes from Vitamin C.
One of the few reactions where we actually have a vitamin that's
playing an important role in a chemical process.
Vitamin C is ultimately the source of this.
We make hydroxyproline and one of the reasons that we have to have
hydroxyproline is so we can make strong collagen, okay?
Now, this was discovered partly, originally, back in the days of
the old pirates.
The pirates would go out.
Big, honking, hairy, stinky, ugly guys going out conquering the
world, killing and robbing and doing all kinds of nasty things,
and they would go out on the ocean for months at a time and they
ate salted meat, because they did have refrigeration.
They didn't exactly have arugula.
They didn't have any fruit desserts.
They had no source of Vitamin C.
And so they'd go out as these big, hunking, ugly guys, and they'd
come back as these puny little wimps.
They'd develop a condition called scurvy.
And that scurvy arises from Vitamin C, and I'm going to tell you
what is involved in scurvy.
What's involved in scurvy?
Well, these hydroxyl groups that we put onto proline
are very important.
Because it turns out that these hydroxyl groups are reactive with
each other such that, when we start putting them together, they'll
make bonds with each other.
We can actually tie these strands together with covalent bonds that
arise from those hydroxyl groups on proline.
If you ever braid your hair, you've got to tie it off with something
on the bottom, right?
Otherwise, the braid falls out.
These chemical bonds that form between the hydroxyls are actually
linking those strands together and keeping them from falling apart,
and giving strength to the collagen.
As a result of Vitamin C, you have strong collagen.
You don't fall apart.
If you don't have Vitamin C, you develop scurvy, you have weak
collagen, and, literally, you fall apart.
That's what happens with them.
I was going to sing a song, but I think we will call it a day and
save that for another time.
See you guys on Wednesday.
How you doing?
Student: Are there any other hydrophobic amino acids
that form zippers?
Or is it just leucine?
Kevin Ahern: Leucine zippers are the best well-known ones.
Student: Okay.
Kevin: That's a good question.
[no audio]
Kevin: [laughs] I should write one, I suppose, shouldn't I?
Captioning provided by Disability Access Services
at Oregon State University.