3N94

Crystal structure of human pituitary adenylate cyclase 1 Receptor-short N-terminal extracellular domain

Summary for 3N94

• Entry DOI: 10.2210/pdb3n94/pdb
• Related PRD ID: PRD_900001
• Descriptor: Fusion protein of Maltose-binding periplasmic protein and pituitary adenylate cyclase 1 Receptor-short, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, SULFATE ION, ... (4 entities in total)
• Functional Keywords: g-protein coupled receptor, mbp fusion protein, membrane receptor, peptide hormone receptor
• Biological source: Escherichia coli; More
• Total number of polymer chains: 1
• Total formula weight: 53175.82

Authors

Kumar, S.,Pioszak, A.A.,Swaminathan, K.,Xu, H.E. (deposition date: 2010-05-28, release date: 2011-06-08, Last modification date: 2024-10-16)

Primary citation

Kumar, S.,Pioszak, A.,Zhang, C.,Swaminathan, K.,Xu, H.E.
Crystal Structure of the PAC1R Extracellular Domain Unifies a Consensus Fold for Hormone Recognition by Class B G-Protein Coupled Receptors.
Plos One, 6:e19682-e19682, 2011

PubMed Abstract: Pituitary adenylate cyclase activating polypeptide (PACAP) is a member of the PACAP/glucagon family of peptide hormones, which controls many physiological functions in the immune, nervous, endocrine, and muscular systems. It activates adenylate cyclase by binding to its receptor, PAC1R, a member of class B G-protein coupled receptors (GPCR). Crystal structures of a number of Class B GPCR extracellular domains (ECD) bound to their respective peptide hormones have revealed a consensus mechanism of hormone binding. However, the mechanism of how PACAP binds to its receptor remains controversial as an NMR structure of the PAC1R ECD/PACAP complex reveals a different topology of the ECD and a distinct mode of ligand recognition. Here we report a 1.9 Å crystal structure of the PAC1R ECD, which adopts the same fold as commonly observed for other members of Class B GPCR. Binding studies and cell-based assays with alanine-scanned peptides and mutated receptor support a model that PAC1R uses the same conserved fold of Class B GPCR ECD for PACAP binding, thus unifying the consensus mechanism of hormone binding for this family of receptors.

PubMed: 21625560
DOI: 10.1371/journal.pone.0019682

Experimental method

X-RAY DIFFRACTION (1.8 Å)