SL+D103+lecture+12+Signaling+IIIa

SL+D103+lecture+12+Signaling+IIIa - D103: Cell Biology Dr....

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D103: Cell Biology Dr. Shin Lin
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Lecture 12 Signaling III: G Proteins
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Page 3 D103 Fall 2011 Lecture 12 - Trimeric G-protein coupled receptors a seven a -helix ‘serpentine’ transmembrane receptor a hetero-trimeric G -protein Recommended Reading: MBOC 5e, pages 904 - 921 1. G-Protein Coupled Receptors (GPCR) First, the 2 main characters in this story: 2. G Protein (Hetero-trimeric GTPase)
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Page 4 A third member of the cast in this movie: 3. Membrane-linked Enzyme/Channel D103 Fall 2011 Lecture 12 - Trimeric G-protein coupled receptors G Protein Coupled Receptor (GPCR) G Protein (Hetero- trimeric GTPase) Membrane-linked Enzyme/Channel
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Page 5 D103 Fall 2011 Lecture 12 - Trimeric G-protein coupled receptors Basic cycle of G-protein signal transduction GPCR movie Now the movie:
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Page 6 D103 Fall 2011 Lecture 12 - Trimeric G-protein coupled receptors Large family of related proteins. Evolved from a common ancestor by gene duplication and divergence. These proteins bind and hydrolyze GTP. While hydrolyzing GTP, these proteins convey a signal to other components of the intracellular signaling apparatus. GTPases participate in many cellular activities : - Membrane traffic , e.g. Arf, Rab , Sar; monomeric GTPase - Nuclear transport , e.g. Ran; monomeric GTPase - Regulation of the cytoskeleton , e.g. Rho; monomeric GTPase - Protein synthesis , e.g. EF-Tu ; monomeric GTPase - Protein translocation in ER , e.g. SRP; monomeric GTPase - Signal transduction , e.g. Ras , monomeric GTPase - Signal transduction , e.g. G a  plus    , heterotrimeric GTPase The Family of GTP-binding proteins (aka GTPases or G-proteins) - what do they do ?
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Page 7 iClicker: G-protein signaling: A. Turns things on in the cell. B. Turns things off in the cell. C. Both depending whether you are looking at the beginning or the end of the pathway. D103 Fall 2011 Lecture 12 - Trimeric G-protein coupled receptors
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Page 8 D103 Fall 2011 Lecture 12 - Trimeric G-protein coupled receptors Components and events of a generic monomeric GTPase cycle - how do they work ? GAP G TPase A ctivating P rotein (greatly increases rate at which GTPase hydrolyses GTP, thus reduces time that GTPase is on ). GEF - G uanine nucleotide E xchange F actor (stimulates exchange of GDP for GTP, helps turn GTPase on ) GDI - G uanine nucleotide D issociation I nhibitor ( prevents loss of GDP from GTPase, helps keep GTPase off ) Inactive Active Note - GDP-bound GTPases do not bind to, or activate effectors without first being activated by GEFs. 1.(step 4) Dissociation of GDP , mediated by a GEF - this is usually the slowest (rate-limiting) step in the cycle. 2.( step 1 ) Binding of GTP - this step is fast . Binding of GTP changes the conformation of three regions of the GTPase (loops, called switch I-III), which fold around the - phosphate of GTP . At the same time, this folding induces a conformational change that forms a binding site on the GTPase for downstream targets
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SL+D103+lecture+12+Signaling+IIIa - D103: Cell Biology Dr....

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