D3BF32FAd01 - Name Section TA 7.012 Problem Set 5 Please...

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Name_____________________________________ Section_______ TA_____________ 1 7.012 Problem Set 5 Please print out this problem set and answer the questions on the printout. Answers to this problem set are to be turned in at the box outside 68-120 by 3:00, Friday Oct 24th. Problem sets will not be accepted late. Solutions will be posted at: http://stellar.mit.edu/S/course/7/fa08/7.012/index.html Question 1 The following is a diagram of a G protein linked receptor that binds to a ligand and activates G proteins. The G proteins in their inactive form remain bound to GDP. However, they exchange GDP for GTP on being activated and dissociate into G α and G βγ subunits. The G α subunit interacts with the adenylate cyclase enzyme which catalyzes the formation of cAMP. The system returns to its inactive state when G α hydrolyzes GTP into GDP. Many different G proteins are present in cells. Some activate adenylate cyclase whereas some inhibit it. a) You are studying the morphine receptor that is an example of a G-protein linked receptor. The wild type morphine receptor possesses four domains: a secretion signal sequence, a transmembrane domain, the ligand binding domain and the cytoplasmic domain shown below. Both the secretion signal sequence and the transmembrane domain act in conjunction to target the protein to plasma membrane. N C signal sequence ligand binding transmembrane Cytoplasmic domain domain domain L C S T
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Name_____________________________________ Section_______ TA_____________ 2 Question 1 continued Using the format that is shown for the structure of wild type receptor protein, identify the domain that is mutated for each of the following mutant receptors (A-D). Assume that each mutant has a deletion in only one domain and that the other domains fold properly. Receptor Location Ligand bound cAMP compared to basal state Mutated domain Wild type Plasma membrane Yes High Mutant A Cytoplasm No Low S Mutant B Plasma membrane No Low L Mutant C Secreted Yes Low T Mutant D Plasma membrane Yes Low C When a functional morphine receptor is expressed in wild type cells, you find the following result. Morphine receptor state G protein status Level of cAMP Receptor alone GDP- G protein 50mmol Receptor - morphine GTP- G α subunit 20mmol b) Based on the results above, outline the steps of morphine signaling pathway beginning with morphine binding to a receptor and ending with the changes in cAMP levels. The morphine receptor is activated by binding to morphine which serves as its ligand. The activated receptor cleaves the G protein to G α and G βγ subunits . The G subunit binds to GTP and is the active form of G proteins. The G -GTP complex then binds to and inhibits the adenylate cyclase enzyme thus reducing the cAMP level. c) To a wild- type cell, expressing the morphine receptor, you add a GTP analog that cannot be
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D3BF32FAd01 - Name Section TA 7.012 Problem Set 5 Please...

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