Essential Cell Biology 5th edition

546 CHAPTER 16 Cell Signaling
Figure 16–15 An activated GPCR
activates G proteins by encouraging
the α subunit to expel its GDP and pick
up GTP. (A) In the unstimulated state,
the receptor and the G protein are both
inactive. Although they are shown here as
separate entities in the plasma membrane,
in some cases they are associated in a
preformed complex. (B) Binding of an
extracellular signal molecule to the receptor
changes the conformation of the receptor,
which in turn alters the conformation of
the bound G protein. The alteration of
the α subunit of the G protein allows it to
exchange its GDP for GTP. This exchange
triggers an additional conformational
change that activates both the α subunit
and a βγ complex, which dissociate to
interact with their preferred target proteins
in the plasma membrane (Movie 16.2). The
receptor stays active as long as the external
signal molecule is bound to it, and it can
therefore activate many molecules of G
protein. Note that both the α and γ subunits
of the G protein have covalently attached
lipid molecules (red ) that help anchor the
subunits to the plasma membrane.
(A)
plasma membrane
EXTRACELLULAR SPACE
CYTOSOL
α
inactive receptor protein
β
GDP γ
signal molecule
inactive G protein
activated receptor
(B)
GDP dissociation
GTP
activated
α subunit
GTP
activated
βγ complex
EFFECTOR ACTIVATION
affinity for GDP, which is then exchanged for a molecule of GTP. In some
cases, this activation breaks up the G-protein subunits, so that the activated
α subunit, clutching its GTP, detaches from the βγ complex, which
ECB5 e16.19/16.15
is also activated (Figure 16–15B). The two activated parts of the G protein—the
α subunit and the βγ complex—can then each interact directly
with target proteins in the plasma membrane, which in turn may relay the
signal to other destinations in the cell. The longer these target proteins
remain bound to an α subunit or a βγ complex, the more prolonged the
relayed signal will be.
The amount of time that the α subunit and βγ complex remain “switched
on”—and hence available to relay signals—also determines how long a
response lasts. This timing is controlled by the behavior of the α subunit.
The α subunit has an intrinsic GTPase activity, and it eventually hydrolyzes
its bound GTP to GDP, returning the whole G protein to its original,
inactive conformation (Figure 16–16). GTP hydrolysis and inactivation
usually occur within seconds after the G protein has been activated. The
inactive G protein is then ready to be reactivated by another activated
receptor.