2jod
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The pituitary adenylate cyclase-activating polypeptide (PACAP) receptor is | + | 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== | ==About this Structure== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Barrett, L | + | [[Category: Barrett, L W.]] |
| - | [[Category: Davis-Taber, R | + | [[Category: Davis-Taber, R A.]] |
| - | [[Category: Hajduk, P | + | [[Category: Hajduk, P J.]] |
| - | [[Category: Lake, M | + | [[Category: Lake, M R.]] |
| - | [[Category: Olejniczak, E | + | [[Category: Olejniczak, E T.]] |
[[Category: Pereda-lopez, A.]] | [[Category: Pereda-lopez, A.]] | ||
| - | [[Category: Richardson, P | + | [[Category: Richardson, P L.]] |
| - | [[Category: Scott, V | + | [[Category: Scott, V E.]] |
| - | [[Category: Solomon, L | + | [[Category: Solomon, L R.]] |
[[Category: Song, D.]] | [[Category: Song, D.]] | ||
[[Category: Sun, C.]] | [[Category: Sun, C.]] | ||
| - | [[Category: Uchic, M | + | [[Category: Uchic, M E.]] |
| - | [[Category: Walter, K | + | [[Category: Walter, K A.]] |
[[Category: protein/peptide complex]] | [[Category: protein/peptide complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:04:40 2008'' |
Revision as of 16:04, 21 February 2008
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Pac1-Rshort N-terminal EC domain Pacap(6-38) complex
Overview
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
2JOD is a Protein complex structure of sequences from Homo sapiens. Full crystallographic 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 Thu Feb 21 18:04:40 2008
