Structural highlights
Function
[PACR_HUMAN] This is a receptor for PACAP-27 and PACAP-38. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. May regulate the release of adrenocorticotropin, luteinizing hormone, growth hormone, prolactin, epinephrine, and catecholamine. May play a role in spermatogenesis and sperm motility. Causes smooth muscle relaxation and secretion in the gastrointestinal tract. [PACA_HUMAN] Binding to its receptor activates G proteins and stimulates adenylate cyclase in pituitary cells.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
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.
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Inooka H, Ohtaki T, Kitahara O, Ikegami T, Endo S, Kitada C, Ogi K, Onda H, Fujino M, Shirakawa M. Conformation of a peptide ligand bound to its G-protein coupled receptor. Nat Struct Biol. 2001 Feb;8(2):161-5. PMID:11175907 doi:http://dx.doi.org/10.1038/84159
- ↑ 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. Solution structure and mutational analysis of pituitary adenylate cyclase-activating polypeptide binding to the extracellular domain of PAC1-RS. Proc Natl Acad Sci U S A. 2007 May 8;104(19):7875-80. Epub 2007 Apr 30. PMID:17470806