So far I’ve talked about receptor systems
that are functioning in fairly general terms.
Let’s take a look up close and personal
now at individual receptor system
known as the G-protein coupled receptors,
or as people refer them, the GPCRs.
The GPCRs are G-protein coupled receptors, are
a very abundant class of receptor proteins.
There’s almost 800 genes in the human genome that are
specifically in the form of G-protein
coupled receptor sequences.
Amazingly, almost 460 of these are olfactory, meaning
that they’re involved in the process of smelling.
So the GPCR depicted here is
embedded in a lipid bilayer.
And we’ve used color to identify the different regions
of the protein projecting through the lipid bilayer.
Though at the bilayer of
course is shown in grey.
The protein embedded in it has the different
colors of blue, green, yellow and red.
We see numbers associated with those and we
see different colors associated with those.
So each change of color represents a
different portion of the protein that’s going
from either down to up, or up to down,
or down to up, and up to down, etcetera.
This protein traverses the lipid bilayer by
moving seven times up and down and up and down.
So those are known as seven transmembrane domains
and that’s where the name 7TM comes from.
We can see that the protein
has two distinct endings.
One ending at the top that has a NH3+,
that’s the amine end of the protein.
And a carboxyl end of the
protein in red at the bottom.
Now, this orientation of the protein and lipid
bilayer is specific for each individual protein.
Now, the β-adrenergic receptor that I want to
talk about is an example of one of the seven TMs,
and it’s involved in working the process of
managing the glycogen metabolism of the cell.
So GPCRs get their name from the fact
that they’re G-protein coupled receptors.
So it’s appropriate I should say a little bit
about what G-proteins are and how they work.
So G-proteins are small proteins that bind to guanine
nucleotides, that’s the G part of their name.
The two different nucleotides that they can bind are known as
GDP or guanosine diphosphate or guanosine triphosphate, GTP.
We see in the example shown on the
screen that the G-protein is shown as
three units - an alpha (α) unit, a
beta (β) unit and a gamma (γ) unit.
This depicts what is called a
And all G-proteins are essentially
heterotrimeric, meaning they have three different
subunits that are not the same in overall
structure; this has the α, the β and the γ.
Now these proteins
associate with GPCRs.
So the G-protein is associating
with this membrane-bound protein.
And they’re associating with it
on the inside part of the cell.
Remember the outside part of the
cell is where the hormone binds,
and the inside part of the cell is
where the G-protein is located.
Now, the G-proteins are actually altered
by the GPCRs binding of hormone.
You remember back in the slide that
I showed you that the binding of
the hormone changed the shape of the
GPCR on the inside of the cell.
It’s that change in shape of the GPCR that actually
changes the G-protein that is associated with it.
And we’ll see that in this slide here.
So the G-protein is associated as we can see,
and it’s what we call the resting state.
The hormone has not bound.
Epinephrine in this case comes and binds
to the G-protein coupled receptor.
And when it does that, it actually changes
the shape of the G-protein coupled receptor.
And I’ve kind of exaggerated
it here by using a pentagon.
The change in shape of the GPCR
causes the interaction between the α
subunit of the G-protein and the β
and the γ subunits that change.
The β and γ subunits are released, and in addition, the
α subunit replaces the GDP that was in it with a GTP.
Now that further facilitates the
release of the γ and the β subunits.
Well, one of the functions of the γ subunit is to
actually help the α subunit to associate with the GPCR.
When the γ subunit has gone away, then the α subunit
is also now free to go away and it’s carrying GTP.
Well GTP is an activation signal, it
means that this individual α subunit
has gotten information from outside the
cell, communicated through the GPCR,
and that α subunit is going to go, and
it’s going to interact with other
proteins, change their behavior and
communicate that signal inside of the cell.
We see that happening here.
So now what’s going to happen is
that the α subunit will interact with
another protein and cause that other
protein to create a second messenger.
So here’s our activated α subunit
with a GTP attached to it.
The protein that the α subunit associates with is
another membrane protein called adenylate cyclase.
When the α subunit with the GTP binds to adenylate
cyclase, adenylate cyclase is also changed.
Now, what’s the change?
Well the blue depiction here of the
adenylate cyclase is the inactive
form of the enzyme, meaning it’s not catalyzing any reaction.
But when it’s car has been changed as we see here, that
indicates that the enzyme has been changed in its activity.
The change in the activity upon binding of the α subunit,
causes production of a molecule known as cyclic AMP.
And we can see the reaction
depicted on the screen here.
ATP is being converted
into cyclic AMP.
And cyclic AMP you may remember from an
earlier slide, is a second messenger.
This small molecule is now going to go to another
part of the cell and cause the effect to be observed.