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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
15
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pubmed:dateCreated |
2007-4-10
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pubmed:abstractText |
Activation of guanine nucleotide-binding protein (G protein)-coupled receptors is believed to involve conformational change that exposes a domain for G protein coupling at the cytosolic surface of the helical confluence, although the mechanisms for achieving this are not well understood. This conformational change can be achieved by docking a diverse variety of agonist ligands, known to occur by interacting with different regions of these receptors. In this study, we focus on the importance of a specific basic residue (Lys187) within the second extracellular loop of the receptor for the peptide hormone, cholecystokinin. Alanine-replacement and charge-reversal mutagenesis of this residue showed that it had no effect on the binding of natural peptide and nonpeptidyl ligands of this receptor but markedly interfered with agonist-stimulated signaling. It was demonstrated that this negative effect on biological activity could be eliminated with the truncation of the first 30 residues of the amino-terminal tail of this receptor. Complementary charge-reversal mutagenesis of each of the five conserved acidic residues within this region of the receptor in the presence of the charge-reversed Lys187 revealed that only the Asp5 mutant fully reversed the negative functional impact of the Lys187 charge reversal. Thus, we have demonstrated that a basic residue within the second extracellular loop of the cholecystokinin receptor interacts with a specific acidic residue within the amino terminus of this receptor. This residue-residue interaction is nicely accommodated within a new molecular model of the agonist-occupied cholecystokinin receptor.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17381074-10555959,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17381074-10581329,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17381074-10595537,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17381074-11050076,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17381074-11961122,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17381074-12362367,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17381074-12910455,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17381074-12916469,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17381074-14722234,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17381074-15322246,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17381074-16451051,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17381074-2479932,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17381074-271968,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17381074-3410633,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17381074-3838314,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17381074-6172156,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17381074-6254391,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17381074-7654246,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17381074-7896869,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17381074-8663161,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17381074-8700154,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17381074-8829180,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17381074-9305898,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17381074-9582333,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17381074-9873689
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0006-2960
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
17
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pubmed:volume |
46
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4522-31
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pubmed:dateRevised |
2010-12-3
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pubmed:meshHeading |
pubmed-meshheading:17381074-Animals,
pubmed-meshheading:17381074-Binding Sites,
pubmed-meshheading:17381074-CHO Cells,
pubmed-meshheading:17381074-Cricetinae,
pubmed-meshheading:17381074-Cricetulus,
pubmed-meshheading:17381074-Lysine,
pubmed-meshheading:17381074-Models, Biological,
pubmed-meshheading:17381074-Models, Molecular,
pubmed-meshheading:17381074-Mutagenesis,
pubmed-meshheading:17381074-Mutation,
pubmed-meshheading:17381074-Peptides,
pubmed-meshheading:17381074-Protein Binding,
pubmed-meshheading:17381074-Protein Structure, Secondary,
pubmed-meshheading:17381074-Receptors, Cholecystokinin,
pubmed-meshheading:17381074-Structure-Activity Relationship
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pubmed:year |
2007
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pubmed:articleTitle |
Role of lysine187 within the second extracellular loop of the type A cholecystokinin receptor in agonist-induced activation. Use of complementary charge-reversal mutagenesis to define a functionally important interdomain interaction.
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pubmed:affiliation |
Cancer Center and Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Scottsdale, Arizona 85259, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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