communication and signalling and transduction by Khuram aziz

4. Signal Reception: G Protein-Coupled Receptors

18. Another Receptor – G Protein Cycle

19. Structure, function and mechanisms of G-Proteins

21. 1994 Nobel Prize in Medicine, Alfred Gilman and Martin Rodbell, for their „discovery of G-Proteins and the role of these proteins in signal transduction in cells.“

22. G-Protein = Guanine-nucleotide binding protein (GNBD) Guanine Ribose Phosphates 1 2 5 4 3 α   1 3 4 2 6 5 7 8 9 Guanosine Ester Anhydride Guanosine-triphosphate - GTP

37.  &  subunits have covalently attached lipid anchors that bind a G-protein to the plasma membrane cytosolic surface. Adenylate Cyclase (AC) is a transmembrane protein, with cytosolic domains forming the catalytic site. The   subunit of a G-protein ( G  ) binds GTP , & can hydrolyze it to GDP + P i .

42. Fig 15.3 The G Protein Cycle

43. G Protein-Linked Receptors

44. G Protein-Linked Receptors

45. G Protein-Linked Receptors

46. G Protein-Linked Receptors note how activation is reversible

47. G Protein-Linked Receptors the more ligand binding, the more K + in cytoplasm

53. How G-protein-coupled receptors work (1) extracellular space cytosol    heterotrimeric G-protein ‘ 7TM’ - receptor GDP GDP GTP Ligand    N

54. How G-protein-coupled receptors work (2) inactive    GDP P active N  GTP   N

55. How G-protein-coupled receptors work (3) ATP inactive inactive active cAMP cAMP Protein kinase A Phosphorylation of multiple target proteins active Adenylate cyclase    GTP

56. Some G-proteins are inhibitory  -Adrenoceptor  2 -Adrenoceptor AC active AC inactive  s GTP  i GTP

57.  -Subunits of G proteins may have regulatory activity, too Muscarinic (M 2 ) acetylcholine receptor K ir AC inactive K +    i GTP

58. G  -proteins regulate diverse effector systems  q phospholipase C  PIP 2 IP 3 + DAG protein kinase C  phosphorylation of multiple proteins Ca ++ ER  t cGMP phosphodiesterase  cGMP   s adenylate cyclase  protein kinase A  cAMP   i1 adenylate cyclase  protein kinase A  cAMP 

59. Many transmitters have multiple GPCR with different downstream signaling mechanisms Norepinephrine,  1 IP 3 + DAG  epinephrine  2 cAMP   1 ,  2 cAMP  Dopamine D 2 - D 4 cAMP  D 1 , D 5 cAMP  Acetylcholine       IP 3 + DAG   2 , M 3 cAMP 