Four levels of protein structure | Chemical processes | MCAT | Khan Academy


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 want
to 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
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 coil-like structure,
just like so, then you’d
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 beta sheet, and
that just looks like this.
It kind of looks more
like a zigzag pattern.

And the 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
bond stabilizing like so,
then you have the amino end
coming around and lining up
with the carboxyl
end, and you have
an anti-parallel 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 kind of 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 interaction, 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 cystines.
So cystines 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.

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 confirmation,
you must have the correct
primary structure,
secondary 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 disease states.

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