Proteins, Levels of Structure, Non-Covalent Forces, Excerpt 1 | MIT 7.01SC Fundamentals of Biology

Proteins, Levels of Structure, Non-Covalent Forces, Excerpt 1 | MIT 7.01SC Fundamentals of Biology


HAZEL SIVE: All right. Let’s move on to the second
topic of our discussion today, which we will start today and
then continue on Friday. And this is a discussion
of the proteins. The proteins, probably the
most fascinating class of macromolecules, 55% of the dry
mass of a cell, and proteins function everywhere. They do almost everything. Strictly speaking, proteins
are not hereditary information, although Professor
Jacks will talk with you about a class of proteins
called prions, which kind of are hereditary information. So not hereditary info,
but they do almost everything else. They form the structure
of the cell. They form a major class of
catalysts called enzymes that we will talk about on Friday. They function in defense as
in the immune system. They allow cells to move,
dot, dot, dot. Okay? We’ll talk about proteins on and
on and on as major players in the fabric of life. Their monomer is an amino
acid that is abbreviated AA or little aa. And it has a particular
structure that forms around a central carbon, which is called
the alpha carbon. And from this alpha carbon,
there are four groups that emanate, something called R,
which is the functional interesting group of
each amino acid. So R is characteristic of each
class of amino acid. We’ll talk more about
this in a moment. And then we’ll put in a hydrogen
and then there is a nitrogen or an amine group,
which I’m going to draw here as NH3 positive. And the other group is a
carboxyl group, which I’m going to draw here
again as ionized. So R, actually, I’m going to
give a special name to. We’ll call it a side chain. And this side chain can
be a charged group. It can be polar or non-polar. And let me see what I have
as the first thing. Yes. Here are some of the side groups
in amino acids, for example, lysine. Here is the alpha carbon, and
here’s its side group. You can see it ends
in an amino group. It’s positively charged. Glutamic acid, I keep forgetting
glutamic acid. This is a better screen. Glutamic acid ends. It’s got a carboxyl
group at the end. It’s negatively charged. It’s an acid. Here’s one, tyrosine with
a polar uncharged group. This benzene ring and the
hydroxyl gives some polarity to the molecule and here’s
leucine with a hydroxyl gives polarity. Leucine is non-polar. It’s really a hydrocarbon and
cystine has this interesting very reactive sulfhydryl group
at the end of its R chain, which is capable of reacting
with another sulfhydryl group and forming a disulfide bond. The polymer, actually I think
I could write it here, the polymer of amino acids looks
like this, and it’s called a peptide if it’s less than 20
amino acids and a protein if it’s about more than
20 amino acids, but that’s kind of loose. You should know the term
peptide, polypeptide mean something a bit bigger than a
peptide, protein, they’re all the same chemical structure — just refers to differences
in the amount of sequence in the polymer. How does the protein
polymer form? I’ll draw that for you now. And it forms by making a
particular bond called a peptide bond that you should
know and be able to recognize. So let’s draw amino acid
one with carbon. And we’re going to put its amino
group, its hydrogren, and then its carboxyl group. And we’re going to add to it. So this is going to be amino
acid one, and we’re going to add to it another one with
a second side chain. And here, we’ll draw out the
hydrogens on the amino group. This oxygen and the hydrogens
on the amino group are going to interact, and they are
going to undergo a condensation reaction. And actually I realize when I
drew for you the nucleotide condensation reaction, that
was when we drew the dinucleotide that was forming,
I realize I didn’t put that there was elimination of a
molecule as the dinucleotide was forming. It’s a bit complicated, and that
was why I didn’t do it. But in this case, this is a kind
of classic condensation reaction, which will eliminate
water, and you’ll end up with something that looks
like this. So here’s your alpha. I’m going to circle the alpha
carbon so we don’t get where they are. And then we’ve got a carbonyl
group that’s joined to an amine and then the other
alpha carbon, R2. So here is amino acid
one, amino acid two. And here is a dipeptide,
or diamino acid. It doesn’t really matter
what you call it. The peptide bond is this guy,
and it’s a very, very important bond. It holds the protein chain
together, and you need to be able to recognize it. Two other features of this
as well, which will be reminiscent of the nucleic acid
case, and on one end — the ends are different. Okay? The ends are different. On one end, there is a free
amino group, and this is called the amino end or the
N-terminal of the dipeptide or of the protein. And on the other end, there is
a free carboxyl group, and this is termed the carboxyl or
the carboxy, or the C-terminal of this dipeptide, or indeed
of any protein. So this is going to sound
reminiscent of the case as in nucleic acids because like
nucleic acids, proteins, because they have different
ends, have a linear order. So we’ll write it again,
different ends and a linear order. And again, it’s this linear
order that can only be read in one direction or that leads
to information that is not symmetric or not randomly
oriented that gives the protein its particular
properties. So let’s write this out
again, formally. On one end, there’s
the amino end. You can also write
this as NH2. It’s done kind of casually. You can write it as N. Doesn’t
really matter to us. And then here’s your polymer
of amino acids. And here is your carboxy end. You can write COO. I always write COOH. You can also write C. All of
those are kind of given as being equivalent and this is
your amino end and your carboxy end. That’s terminology, but you can
tell from where these free chemical groups are which amino
acid was added first and which was added last. And the amino acid nearest the
end terminal is added first. The one nearest the free carboxy
is the most recently added, always added last. Now, we went through a bit of
a calculation for nucleic acids where there are four
bases, and I pointed out to you that you could get a lot of
combinatorics out of four bases if you had a polymer
that was long enough. For proteins, the situation
is actually dauntingly more complex. There are 20 different
amino acids. So for a peptide, that’s three
amino acids, you would get 20 to the third combinations
or 8,000. Proteins can be greater than
1,000 amino acids in length. Proteins or peptides for little
ones can range from two to greater than 1,000
amino acids. And so the number of
combinations of information that you can get in proteins
is enormous, and that means that most of protein space has
not been explored by life and can be explored in
the laboratory. And that’s very exciting in
thinking about the various functions that one can find that
have not yet been found. Now, the thing that is different
about nucleic acids and proteins apart from their
fundamental chemical structure, is that nucleic
acids, as we will discuss, are used as a linear more
or less, they are read as a linear string. You start somewhere, and you
read along the nucleic acid, and you get your information
out, and that gives you some kind of a next step. Proteins, although they have a
linear order, are not used in this kind of straight
linear way. They are read once they
have folded up into three-dimensional structures,
and the folding of proteins into these 3D structures is
intrinsic and essential for their function. So protein folding — Actually, let me before we do
protein folding, I realize I’ve been remiss in giving
you these slides. Here is something I drew
for you on amino acid polymerization from your
book, and here we are where we should be. Protein folding is required
for function. The linear order of amino acids
in the first peptide chain that is synthesized is
called the primary structure. So primary structure refers
to the linear order of amino acids. And these amino acids, of
course, are held together by covalent bonds as in
peptide bonds. But this primary structure,
while absolutely essential for protein function, is not
the functional protein. It folds up, this primary
structure, this linear chain, folds up and folds again
and folds again. The way I think of it is, if you
took a piece of string or an old-fashioned telephone cord,
and you folded it up, you start rolling it up into a
roll, it will roll up, and it’ll fold back on itself, and
fold back on itself, and fold back on itself. And that’s kind of the
deal with proteins. So we have to consider something
called secondary structure where the linear chain
of amino acids folds back on itself. So the linear amino acid
chain folds up, and it does so in two ways. It forms something called an
alpha helix or it forms something called a beta sheet
or a beta pleated sheet, and these are characteristics
folding structure or folding patterns that are governed
by hydrogen bonds. But that secondary structure
of the protein is not the functional protein. Those folded hydrogen-bonded
alpha helices or beta sheets fold on themselves again to form
the tertiary structure of the protein. So this is more folding
of the alpha helices or the beta sheets. And this tertiary structure
can involve any number of different kinds of bonds. It can involve covalent bonds
like sulfhydryl disulfide bonds, hydrogen bonds,
hydrophobic bonds, and all of these things give a tertiary
structure. All of them use one linear
polypeptide or protein chain. But then there’s a fourth
folding that is required for the function of many proteins. This is the quaternary
structure, and this refers to, so again, this is of the primary
and secondary chain. The quaternary structure is
an association between two different proteins in a
non-covalent way, usually. So this is association between
two different protein chains and two different protein chains
that are in some kind of tertiary structure. And usually this association
is non-covalent. The way protein structure is
governed and proteins fold is mysterious, and very
complicated, and not well understood. And there we go. Look at this interesting stuff
you can see on my screen. Here we go. Here, not from your book because
I think it’s better from a different book, is a
picture of an alpha helix, a beta sheet, tertiary structures
of folded polypeptide chains. And here is a quaternary
structure. And as we’ll talk about on
Friday, it’s the quaternary structures that are these
functional units called enzymes, and we’ll stop there.