G protein coupled receptors

This slideshare provides the knowledge on the gpcrs roles and importance ,pathway in eukaryotes...

1. G-PROTEIN COUPLED RECEPTORS Presented by : Rajeshwari Manasa

2. INTRODUCTION HISTORY CLASSIFICATION STRUCTURE MECHANISM PHYSIOLOGY/FUNCTIONS G-PROTEIN MEDIATED PATHWAYS CONCLUSION CONTENTS :-

3. G-protein Coupled Receptors (GPCRS) are the largest and more diverse group of membrane receptors in eukaryotes . There are large family of cell membrane receptors which are linked to the effector through one/more G-T-P activated for response effectuation. INTRODUCTION :-

4. In 2012, Robert lef kowitz and brian kobilka won the nobel prize in chemistry for ground breaking discoveries that reveal the inner workings of an important family of G-protein coupled receptors . HISTORY :-

5. Based on sequence homology and functional similarity…. ClassA (or)1-Rhodopsin like receptors ClassB (or)2-secretin family ClassC (or)3-metabotropic glutamate receptors ClassD (or)4-fungal mating phermone receptors ClassE (or)5-cyclic AMP receptors ClassF (or)6-frizzled and smoothened receptors CLASSIFICATION :-

6. Based on phylogenetic origin the G-protein coupled receptor classification system has been proposed as : 1.Glutamates 2.Rhodopsin 3.Adhesion 4.Frizzled/Taste 5.secretin

7. All receptors hve a common pattern of structural organisation . Molecule has 1α-helical membrane spanning hydrophobic aminoacid segments which run into 3 entracellular and 3 intracellular loops . STRUCTURE

8. The agonist binding site is located somewhich between on the entracellular face ; which another recognization site formed by cytosolic segments binds the coupling G-protein . The G-protein float in the membrane with there exposed domain lying in the cytosol and are heterotrimeric in composition of α,ß and Γ sub units . In the inactive state GDP is bound to the α sub unit at the exposed domain activation through the receptor leads to displacement of GDP by GTP . MECHANISM

9. The activated α-sub unit carrying GTP dissociates from the other two subunits and either activates or inhibits the effector . The ßΓ ( beta,gamma ) dimer has also been shown to active receptor-operated K+ channels, to inhibit volated gated Ca2+ channels and to promote GPCR(G-protein coupled receptors) descmitization at higher rate of activation

10. A number of G proteins distinguished by the α-sub units has been describes the important ones with their action on the effector are Gs: Adenylyl cyclase activation,ca+2 channel Gi : Adenylyl cclase inhibition,K+channel Go:Ca2+ channel inhibitor Gq:phospholipase c activation

11. The adenylyl cyclase increase CAMP pathway CAMP is a nucleotide Synthesized with in the cell from ATP by membrane bound adenylyl cyclase . Produced continously . Inactivated by hydrolysis to 5′-AMP,by the phospho diesterase . Common mechanisms , namely the activation of protein kinase . PATHWAYS

12. Involved in :- Energy metabolism Cell division and differentiation Ion transport , ion channels Contractile proteins in smooth muscle

13. Phospholipases c:- IP3-DAG pathway:- Activation of phospholipase Cß ( PLCß ) by the activated GTP carrying α subunit of Gq hydrolyses.the membrane phospholipids phosphotidyl ionsitol4,5-bis phosphate(PIP2) to generate the second messengers inositol 1,4,5-triphosphate(IP3) and diacylglycerol (DAG). The IP3 being water soluble diffuses to the cytosol and mobilizer ca+2 from endoplasmic reticulum depots .

14. But the lipophilic DAG remains within the membrane but recruits protein kinase C. Activates it with the help of ca+2 The activated PKc phosphorylates many intracellular proteins(depending on the type of effector cells and mediates various physiological responses). So that it can serve signalling functions,the cytosolic concentrations of ca+2 is kept very low(≈100nm) by specific pumps located at the plasma membrane and at the endoplasmic reticulum. Triggered by IP3, the released ca+2 acts on a highly versatile regulator acting through calmodulin (CAM), Pkcand other effectirs .

15. The activated G-proteins ( Gs,Gi,Go ) can also open or inhibit ionic channels specific for ca2+ and k+, without the intervention of any second messengers like cAMP or IP3. The bring about hyperpolarization /depolarization changes in intracellular ca+2 concentrations. The Gs opens ca2+ channels in myocardium and skeletal muscles, which Gi and Go open k+ channels in heart ans smooth muscles as well as inhibit neuronal ca2+ channels . Channel regulation

16. Direct channel regulation is mostly the functions of the ß^ dimer of the dissociated Gprotein physiological responses like changes in inotopy , chronotropy , transmitter release, neuronal activity and smooth muscle relaxation follow. Receptors found to regulate ionic channels through G-proteins.

17. Visual sense taste and smell Behavioural and mood regulation Immune system activity and inflammation Ans transmission Apoptosis Physiological roles

18. GPCRS are a large family of cell surface that respond to a variety of external signals. Binding of a signaling molecule to a GPCR results in G protein activation, which in turn triggers the production of any number of second messengers Conclusion

19. Essentials of medical pharmacology by KD Tripathi … https://www.nature.com>topicpage. REFERENCES