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New page: left|200px<br /> <applet load="2jod" size="450" color="white" frame="true" align="right" spinBox="true" caption="2jod" /> '''Pac1-Rshort N-terminal EC domain Pacap(6-38...
 
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[[Image:2jod.gif|left|200px]]<br />
<applet load="2jod" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2jod" />
'''Pac1-Rshort N-terminal EC domain Pacap(6-38) complex'''<br />


==Overview==
==Pac1-Rshort N-terminal EC domain Pacap(6-38) complex==
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.
<StructureSection load='2jod' size='340' side='right'caption='[[2jod]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2jod]] is a 2 chain structure with sequence from [https://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]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JOD FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 1 model</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2jod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jod OCA], [https://pdbe.org/2jod PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jod RCSB], [https://www.ebi.ac.uk/pdbsum/2jod PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jod ProSAT]</span></td></tr>
</table>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jo/2jod_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2jod ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


==About this Structure==
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<ref>PMID:17470806</ref>
2JOD is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2JOD OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17470806 17470806]
</div>
<div class="pdbe-citations 2jod" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Hormone|Hormone]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Barrett, L.W.]]
[[Category: Barrett LW]]
[[Category: Davis-Taber, R.A.]]
[[Category: Davis-Taber RA]]
[[Category: Hajduk, P.J.]]
[[Category: Hajduk PJ]]
[[Category: Lake, M.R.]]
[[Category: Lake MR]]
[[Category: Olejniczak, E.T.]]
[[Category: Olejniczak ET]]
[[Category: Pereda-lopez, A.]]
[[Category: Pereda-lopez A]]
[[Category: Richardson, P.L.]]
[[Category: Richardson PL]]
[[Category: Scott, V.E.]]
[[Category: Scott VE]]
[[Category: Solomon, L.R.]]
[[Category: Solomon LR]]
[[Category: Song, D.]]
[[Category: Song D]]
[[Category: Sun, C.]]
[[Category: Sun C]]
[[Category: Uchic, M.E.]]
[[Category: Uchic ME]]
[[Category: Walter, K.A.]]
[[Category: Walter KA]]
[[Category: protein/peptide complex]]
 
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