True about G protein coupled receptors is

True about G protein coupled receptors
is:
a) G proteins bind to hormones on the cell surface
b) All the three subunits alpha, beta and gamma should bind to
each other for G protein to act
c) G proteins act as inhibitory and excitatory because of difference
in alpha subunit
d) G protein is bound to GTP in resting state
Correct Answer - C
G proteins act as inhibitory and excitatory because of difference in
alpha subunit [Ref: Harper 26/e p458; Lippincott Biochem 3/e p93;
Ganong 22/e p41]
G-protein coupled receptors (GPCR) are the largest superfamily of
cell surface receptors.
They typically have seven helices that traverse the membrane.
These receptors are integral membrane proteins characterized by
an extracellular ligand-binding region, seven transmembrane
helices, and an intracellular domain that interacts with G-proteins.
The function of GPCR is to transduce signals that induce a cellular
response to the environment.
Mechanism:
The ligand binds to a site on the extracellular portion of the receptor.
Binding of the ligand to the receptor

  • activates a G protein associated with the cytoplasmic C-terminal.
    This initiates the production of a “second messenger”. The most
    common of these are
  • cyclic AMP, (cAMP) which is produced by adenylyl cyclase from
    ATP and
  • inositol 1,4,5-trisphosphate (IP3)
    The second messenger, in turn, initiates a series of intracellular
    events such as
  • phosphorylation and activation of enzymes
  • release of Ca2+ into the cytosol from stores within the endoplasmic
    reticulum
    G proteins
    G proteins are so-called because they bind the guanine nucleotides
    GDP and GTP. They are heterotrimers (i.e., made of three different
    subunits)
    The three subunits are:
  • Ga, which carries the binding site for the nucleotide. At least 21
    different kinds of Ga molecules are found in mammalian cells.
  • GP
  • Gy
    How They Work
    In the inactive state G protein has GDP bound to its Ga. subunit.
    When a hormone or other ligand binds to the associated GPCR the
    GDP is exchanged for GTP
    GTP activates Ga causing it to dissociate from GI3Gy (which remain
    linked as a dimer).
    Activated Ga in turn activates an effector molecule (adenylyl
    cyclase- an enzyme in the inner. sface of the plasma membrane
    which catalyzes the conversion of ATP into the “second messenger”
    cyclic AMP).
    The beta and gamma subunit do not separate from each other, and
    Gi3Gy dimer also activates a variety of effectors.
    The actions of the Ga-GTP complex are short lived because the G-
    protein has an inherent GTPase activity, resulting in the rapid
    hydrolysis of GTP to GDP. This leads to reassociation of the Ga unit
    with the GI3Gy dimer. This inactivates the G protein.
    The ability of a ligand to stimulate or inhibit the second messenger
    depends on the type of G-protein that is linked to the receptor. One
    family of G-proteins, designated Gs, is specific for stimulation of
    adenylyl cyclase; another family, designated Gi, causes inhibition of
    the enzyme. These different actions of G proteins are attributed to
    different alpha subunits. Gs contains a, and Gi contains
    Some Types of Ga Subunits
    Gas_This type stimulates (s = “stimulatory”) adenylyl cyclase. Gas is
    the target of the toxin liberated by Vibrio cholerae, the bacterium that
    causes cholera. Binding of cholera toxin to Gas keeps it turned “on”.
    The resulting continuous high levels of cAMP causes a massive loss
    of salts from the cells of the intestinal epithelium. Massive amounts
    of water follow by osmosis causing a diarrhea that can be fatal if the
    salts and water are not quickly replaced.
    Ga;-This inhibits (i = “inhibitory”) adenylyl cyclase lowering the level
    of cAMP in the cell.
    Gag_This activates phospholipase C (PLC) which generates the
    second messengers:
  • inositol trisphosphate (IP3)
  • diacylglycerol (DAG)
    Gat_The “t” is for transducin, the molecule responsible for
    generating a signal in the rods of the retina in response to light.