- [Lecturer] So why is it so important
to learn about protein structure?
Well, let's take the example of Alzheimer's disease,
which affects the brain.
So in certain people, as they age,
proteins and their neurons start to become misfolded
and then form aggregates outside of the neurons,
and this is called amyloid.
So amyloid is really just clumps of misfolded proteins
that look a bit like this.
And as you can see, as this amyloid builds up,
it starts to interfere with the neuron's ability
to send messages and this leads to dementia and memory loss.
So, if we can understand how these proteins
become misfolded in the first place,
then we might be able to find a cure
for this debilitating disease.
And to understand how proteins become misfolded
we must first understand how they become properly folded.
So before we begin, I just wanna do a quick review of terms,
you can have one amino acid,
so I'll just write aa for amino acid,
and then you can have two amino acids,
that are linked together by a peptide bond,
so this is a peptide bond.
And as you add more and more amino acids
to this chain of amino acids you start
to get what is called a polypeptide
or many peptide bonds.
And each amino acid, within this polypeptide,
is then termed a residue.
And then proteins consist of one or more polypeptides.
And so I will use the terms polypeptide
and protein interchangeably.
So, at the most basic level, you have primary structure
and primary structure just describes the linear sequence
of amino acids and it is determined
by the peptide bond linking each amino acid.
So if I were to take my amyloid example
from Alzheimer's disease, and I stretch out
that protein all the way,
then this linear sequence is just the primary structure.
So then, moving on, we have secondary structure
and secondary structure just refers to the way
that the linear sequence of amino acids folds upon itself.
This is determined by backbone interactions.
And this is determined primarily by hydrogen bonds.
There are two motifs that, or patterns,
that you should be familiar with,
the first of which is called an alpha helix,
and if you were to take this polypeptide
and wrap it around itself into a coiled-like structure,
just like so, then you would have the alpha helix
and the hydrogen bonds just run up and down,
stabilizing this coiled structure.
And another motif or pattern that you can be familiar with
is with a a beta sheet
and that just looks like this,
it kinda looks more like a zigzag pattern.
And these beta sheet is stabilized
by hydrogen bonds, just like so.
And if you have the amino ends
and the carboxyl ends line up, like so,
then this sheet is called a parallel beta sheet.
And then, conversely, if you have a single polypeptide
that is then wrapping up upon itself just like this
and you have the hydrogen bonds stabilizing, like so,
then you have the amino end coming around
and lining up with the carboxyl end
and you have a antiparallel configuration.
There is a third level of protein structure
called tertiary structure and tertiary structure
just refers to a higher order of folding
within a polypeptide chain.
And so you can kinda think of it as the many different folds
within a polypeptide, which then fold upon each other again.
And so this depends on distant group interactions,
so distant interactions.
And just like secondary structure,
it is stabilized by hydrogen bonds,
but you also have some other interactions
that come into play, such as van der Waals interactions,
you also have hydrophobic packing
and also disulfide bridge formation.
So if we explore hydrophobic packing
just a little bit more over here,
say we have a folded-up polypeptide or protein
and this protein is found within
the watery polar environment of the interior of a cell,
so if we have water on the exterior of this protein,
then we will find all of the polar groups
on the exterior, interacting with this water.
And then, on the interior, you would find the nonpolar,
or hydrophobic groups, hiding from the water.
Disulfide bridges, on the other hand,
describe an interaction that happens only between cysteines.
So cysteines are a type of amino acid
that have a special thiol group as part of its side chain.
And this thiol group has a sulfur atom
that can become oxidized
and when this oxidation occurs
you get the formation of a covalent bond
between the sulfur groups.
The formation of a disulfide bridge happens
on the exterior of a cell
and you tend to see the formation
of separated thiol groups on the interior of a cell.
And that is because the interior of the cell
has antioxidants, which generate a reducing environment.
And since the exterior of a cell
lacks these antioxidants you get an oxidizing environment.
So if I were to ask you which environment
favors the formation of disulfide bridges,
you would say the extracellular space does.
Then there is one final level of protein structure
and that is called quaternary structure
and quaternary structure describes the bonding
between multiple polypeptides.
Multiple polypeptides.
The same interactions that determine tertiary structure
play a role in quaternary structure.
And so let's say I have one folded-up polypeptide,
two folded-up polypeptides and a third and a fourth.
The quaternary structure is described
by the interactions between these four polypeptides
and within the completed protein structure,
each individual polypeptide is termed a subunit.
Since this protein has four subunits,
it is called a tetramer,
and so if I were to have two subunits
it would be called a dimer,
three would be called a trimer
and then anything above four is called a multimer.
So the term for a completely, properly folded-up protein
is called the proper conformation of a protein
and to achieve the proper conformation
you must have the correct primary structure,
second structure, tertiary structure
and quaternary structure,
and if any of these levels of protein structure
were to break down, then you start to have misfolding,
which can then contribute to any
of a number of diseased states.