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2jod

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[[Image:2jod.jpg|left|200px]]
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{{STRUCTURE_2jod| PDB=2jod | SCENE= }}
{{STRUCTURE_2jod| PDB=2jod | SCENE= }}
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'''Pac1-Rshort N-terminal EC domain Pacap(6-38) complex'''
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===Pac1-Rshort N-terminal EC domain Pacap(6-38) complex===
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==Overview==
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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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(as it appears on PubMed at http://www.pubmed.gov), where 17470806 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17470806}}
==About this Structure==
==About this Structure==
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2JOD is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JOD OCA].
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2JOD is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JOD OCA].
==Reference==
==Reference==
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[[Category: Walter, K A.]]
[[Category: Walter, K A.]]
[[Category: Protein/peptide complex]]
[[Category: Protein/peptide complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 17:34:29 2008''

Revision as of 14:34, 28 July 2008

Image:2jod.png

Template:STRUCTURE 2jod

Pac1-Rshort N-terminal EC domain Pacap(6-38) complex

Template:ABSTRACT PUBMED 17470806

About this Structure

2JOD is a Protein complex structure of sequences from Homo sapiens. Full experimental information is available from OCA.

Reference

Solution structure and mutational analysis of pituitary adenylate cyclase-activating polypeptide binding to the extracellular domain of PAC1-RS., Sun C, Song D, Davis-Taber RA, Barrett LW, Scott VE, Richardson PL, Pereda-Lopez A, Uchic ME, Solomon LR, Lake MR, Walter KA, Hajduk PJ, Olejniczak ET, Proc Natl Acad Sci U S A. 2007 May 8;104(19):7875-80. Epub 2007 Apr 30. PMID:17470806

Page seeded by OCA on Mon Jul 28 17:34:29 2008

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