2JOD

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

Summary for 2JOD

• Entry DOI: 10.2210/pdb2jod/pdb
• NMR Information: BMRB: 15166
• Descriptor: Pituitary adenylate cyclase-activating polypeptide type I receptor, Pituitary adenylate cyclase-activating polypeptide (2 entities in total)
• Functional Keywords: protein-peptide complex, signaling protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 16026.24

Authors

Olejniczak, E.T.,Sun, C.,Song, D.,Davis-Taber, R.A.,Barrett, L.W.,Scott, V.E.,Richardson, P.L.,Pereda-lopez, A.,Uchic, M.E.,Solomon, L.R.,Lake, M.R.,Walter, K.A.,Hajduk, P.J. (deposition date: 2007-03-07, release date: 2007-05-22, Last modification date: 2024-11-27)

Primary citation

Sun, C.,Song, D.,Davis-Taber, R.A.,Barrett, L.W.,Scott, V.E.,Richardson, P.L.,Pereda-Lopez, A.,Uchic, M.E.,Solomon, L.R.,Lake, M.R.,Walter, K.A.,Hajduk, P.J.,Olejniczak, E.T.
Solution structure and mutational analysis of pituitary adenylate cyclase-activating polypeptide binding to the extracellular domain of PAC1-RS.
Proc.Natl.Acad.Sci.Usa, 104:7875-7880, 2007

PubMed Abstract: 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.

PubMed: 17470806
DOI: 10.1073/pnas.0611397104

Experimental method

SOLUTION NMR