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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
30
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pubmed:dateCreated |
1995-9-5
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pubmed:abstractText |
Each G protein-coupled receptor can interact only with a limited number of the many structurally similar G proteins expressed within a cell. This study was undertaken to identify single amino acids required for selectively coupling the m3 muscarinic acetylcholine receptor to G proteins of the Gq/11 family. To this goal, distinct intracellular segments/amino acids of the m3 receptor were systematically substituted into the structurally closely related m2 muscarinic receptor, which couples to Gi/o proteins, not Gq/11 proteins. The resultant mutant receptors were expressed in COS-7 cells and studied for their ability to induce agonist-dependent stimulation of phosphatidylinositol hydrolysis, a response known to be mediated by G proteins of the Gq/11 class. Using this approach, we were able to identify four amino acids in the second intracellular loop and four amino acids at the C terminus of the third intracellular loop of the m3 muscarinic receptor that are essential for efficient Gq/11 activation. We could demonstrate that these amino acids, together with a short segment at the N terminus of the third intracellular loop, fully account for the G protein coupling preference of the m3 muscarinic receptor. Taken together, our data strongly suggest that only a limited number of amino acids, located on different intracellular regions, are required to determine the functional profile of a given G protein-coupled receptor.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amino Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Carbachol,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositols,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Muscarinic
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
28
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pubmed:volume |
270
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
17741-8
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pubmed:dateRevised |
2004-11-17
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pubmed:meshHeading |
pubmed-meshheading:7629074-Amino Acid Sequence,
pubmed-meshheading:7629074-Amino Acids,
pubmed-meshheading:7629074-Animals,
pubmed-meshheading:7629074-Carbachol,
pubmed-meshheading:7629074-Cell Line,
pubmed-meshheading:7629074-GTP-Binding Proteins,
pubmed-meshheading:7629074-Humans,
pubmed-meshheading:7629074-Hydrolysis,
pubmed-meshheading:7629074-Molecular Sequence Data,
pubmed-meshheading:7629074-Mutagenesis, Site-Directed,
pubmed-meshheading:7629074-Phosphatidylinositols,
pubmed-meshheading:7629074-Receptors, Muscarinic,
pubmed-meshheading:7629074-Sequence Alignment
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pubmed:year |
1995
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pubmed:articleTitle |
Mapping of single amino acid residues required for selective activation of Gq/11 by the m3 muscarinic acetylcholine receptor.
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pubmed:affiliation |
Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA.
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pubmed:publicationType |
Journal Article
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