G protein-coupled receptors

The GPCRs (G protein-coupled receptors) form a very big collection of cell surface receptors which are coupled to signal-transducing trimeric G proteins. Overall GPCRs hold seven membrane-spanning α-helical regions with their N-terminus on the extracellular face of the plasma membrane and their C-terminus on the cytoplasmic   face. The   GPCR   family   involves   receptors   for numerous hormones and neurotransmitters, light-activated receptors (rhodopsins) in the eye and thousands of odorant receptors in the mammalian nose. On the binding its ligand, a GPCR activates the signal-transducing trimeric G proteins guanyl nucleotide (GTP)-binding proteins that in turn activate or inhibit an effector protein.  Trimeric G proteins consist of three subunits that are:  α, β or γ. The Gα subunit is a GTPase trigger protein which alternates among an active (on) state

Figure:G protein-coupled receptors (GPCRs) contain seven transmembrane  -helical regions (cylinders 1-7), with their N-terminus on the extracellular side of the membrane and their C- terminus in the cytosol.

and an inactive off state. In humans genome there are several copies of every of the α, β or γ subunits, giving diversity in the signaling by GPCRs.

The  Gα and  Gγ subunits  are  connected  to  the  cytosolic  surface  of  the  plasma membrane  through  covalently  connected  lipids.  In the resting state when no ligand is bound to the GPCR the Gα subunit is connect to GDP and hard by Gβγ. Binding of the ligand to the GPCR modifies its conformation causing it to bind to the Gα subunit in like a way which the GDP is displaced and GTP becomes bound. The Gα subunit then dissociates by Gβγ but both remain anchored to the membrane.  The Gα subunit  with GTP bound then interacts with and activates an related effector protein, like as adenylyl cyclase,  or  in  some  cases  regulates  the  opening  of  an  ion  channel  causing  a modifies in the membrane potential. Moreover, this activation is short-lived, as the GTP  is  quickly within  seconds,  hydrolyzed  to  GDP  through  the  intrinsic  GTPase activity in the Gα subunit. The Gα subunit, now with GDP bound dissociates from the effector protein and deactivating it, and reassociates with Gβγ and ready for another round of activation and nucleotide replace in the given figure.

The hormone epinephrine binds to several different GPCRs. On binding to - adrenergic receptors on the surface of adipose and liver cells, epinephrine promotes glycogenolysis and lipolysis,  in that order. On

                     Figure: Signal transduction through a G protein-coupled receptor (see text for details).

smooth muscle cells lining the blood vessels in the skin, kidneys, and intestine epinephrine  binds to the   2-adrenergic  receptor causing the arteries to constrict. β-adrenergic receptors are coupled to the stimulatory G protein (Gs) which activates the membrane-bound adenylyl cyclase, while the α1-adrenergic  receptor is coupled  to an inhibitory  G protein  (Gi) which inhibits adenylyl  cyclase, although the Gq  protein coupled to the α2-adrenergic  receptor activates a various effector protein.  Therefore by  binding  to various  receptors  and activating  several  G proteins  one ligand can switch a variety  of various  actions  in various  target cells.