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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
19
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pubmed:dateCreated |
2007-5-9
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pubmed:databankReference |
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pubmed:abstractText |
The pituitary adenylate cyclase-activating polypeptide (PACAP) receptor is a class II G protein-coupled receptor that contributes to many different cellular functions including neurotransmission, neuronal survival, and synaptic plasticity. The solution structure of the potent antagonist PACAP (residues 6'-38') complexed to the N-terminal extracellular (EC) domain of the human splice variant hPAC1-R-short (hPAC1-R(S)) was determined by NMR. The PACAP peptide adopts a helical conformation when bound to hPAC1-R(S) with a bend at residue A18' and makes extensive hydrophobic and electrostatic interactions along the exposed beta-sheet and interconnecting loops of the N-terminal EC domain. Mutagenesis data on both the peptide and the receptor delineate the critical interactions between the C terminus of the peptide and the C terminus of the EC domain that define the high affinity and specificity of hormone binding to hPAC1-R(S). These results present a structural basis for hPAC1-R(S) selectivity for PACAP versus the vasoactive intestinal peptide and also differentiate PACAP residues involved in binding to the N-terminal extracellular domain versus other parts of the full-length hPAC1-R(S) receptor. The structural, mutational, and binding data are consistent with a model for peptide binding in which the C terminus of the peptide hormone interacts almost exclusively with the N-terminal EC domain, whereas the central region makes contacts to both the N-terminal and other extracellular parts of the receptor, ultimately positioning the N terminus of the peptide to contact the transmembrane region and result in receptor activation.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-10095088,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-10212987,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-10390648,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-10431211,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-10835102,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-10889020,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-10889021,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-10913300,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-11013258,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-11175907,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-11206074,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-11329057,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-11425856,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-11603952,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-11895078,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-12220741,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-12524435,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-12529932,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-12565051,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-12580598,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-1327769,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-4202581,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-7598720,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-7875313,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-8477187,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17470806-9846877
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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 |
May
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pubmed:issn |
0027-8424
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pubmed:author |
pubmed-author:BarrettLeo WLW,
pubmed-author:Davis-TaberRachel ARA,
pubmed-author:HajdukPhilip JPJ,
pubmed-author:LakeMarc RMR,
pubmed-author:OlejniczakEdward TET,
pubmed-author:Pereda-LopezAnaA,
pubmed-author:RichardsonPaul LPL,
pubmed-author:ScottVictoria EVE,
pubmed-author:SolomonLarry RLR,
pubmed-author:SongDanyingD,
pubmed-author:SunChaohongC,
pubmed-author:UchicMarie EME,
pubmed-author:WalterKarl AKA
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pubmed:issnType |
Print
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pubmed:day |
8
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pubmed:volume |
104
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7875-80
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:17470806-Amino Acid Sequence,
pubmed-meshheading:17470806-Animals,
pubmed-meshheading:17470806-Humans,
pubmed-meshheading:17470806-Mice,
pubmed-meshheading:17470806-Molecular Sequence Data,
pubmed-meshheading:17470806-Mutation,
pubmed-meshheading:17470806-Pituitary Adenylate Cyclase-Activating Polypeptide,
pubmed-meshheading:17470806-Protein Structure, Secondary,
pubmed-meshheading:17470806-Protein Structure, Tertiary,
pubmed-meshheading:17470806-Receptors, Corticotropin-Releasing Hormone,
pubmed-meshheading:17470806-Receptors, Pituitary Adenylate Cyclase-Activating...,
pubmed-meshheading:17470806-Solutions
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pubmed:year |
2007
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pubmed:articleTitle |
Solution structure and mutational analysis of pituitary adenylate cyclase-activating polypeptide binding to the extracellular domain of PAC1-RS.
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pubmed:affiliation |
Global Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, IL 60064, USA.
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pubmed:publicationType |
Journal Article
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