G protein-coupled receptors

basic intro to GPCR

1. G-Protein-Coupled Receptors Meenakshi Gupta M.Pharm . 2 nd sem. (Pharmacology )

2. Contents Introduction GPCR- basics & structure Types GPCR mediated pathways

3. Introduction Receptors are the sensing elements in the system of chemical communications that coordinates the function of all the different cells in the body. The chemical messengers can be hormones, transmitters and other mediators.

4. Types of receptors

5. GPCRs The G protein-coupled receptor (GPCR) super family comprises the largest and most diverse group of proteins in mammals. Synonym: “seven-trans-membrane” (7-TM), “serpentine” receptors,  hepta -helical receptors and G protein–linked receptors  (GPLR). The human genome encodes >800 GPCRs.

6. GPCRs  It is involved in information transfer (signal transduction) from outside the cell to the cellular interior. GPCRs are responsible for every aspect of human biology from vision, taste, sense of smell, sympathetic and parasympathetic nervous functions, metabolism, and immune regulation to reproduction.  ~45% of all pharmaceutical drugs are known to target GPCRs.

7. Structure of G protein coupled receptor

8. 7 trans membrane helices connected by alternating cytosolic and extra cellular loop C terminal: inside the cell N terminal : extra cellular region Extra cellular portion has unique messenger binding site Cytosolic loop allow receptor to interact with G protein. G protein contain 3 different subunits: G -Alpha G –Beta G -Gamma G alpha – largest , binds to GTP or GDP G beta & G gamma permanently bound together

9. Act like MOLECULAR SWITCHES ON – when bind to GTP OFF – when bind to GDP When G alpha bind to GTP it detaches from beta and gamma complex

10. When a messenger bind to GPCR the receptor change its conformation G alpha releases its bound GDP and acquires a new molecule of GTP G alpha detaches from G beta & G gamma complex Either the GTP-G alpha subunit or G beta gamma can initiate signal transduction

11. Types of G Proteins

12. G Protein Mediated Pathways A denylyl cyclase : cAMP Pathway Phospholipase C: IP3-DAG Pathway Channel regulation

13. Phospholipase C: IP3-DAG Pathway

14. Channel regulation

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