7WBJ

Cryo-EM structure of N-terminal modified human vasoactive intestinal polypeptide receptor 2 (VIP2R) in complex with PACAP27 and Gs

Summary for 7WBJ

• Entry DOI: 10.2210/pdb7wbj/pdb
• EMDB information: 32401
• Descriptor: Vasoactive intestinal polypeptide receptor 2, Pituitary adenylate cyclase-activating polypeptide 27, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, ... (6 entities in total)
• Functional Keywords: vasoactive intestinal polypeptide receptor 2, g protein-coupled receptor, ligand recognition, structural protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 164981.65

Authors

Xu, Y.N.,Feng, W.B.,Zhou, Q.T.,Liang, A.Y.,Li, J.,Dai, A.T.,Zhao, F.H.,Yan, J.H.,Chen, C.W.,Li, H.,Zhao, L.H.,Xia, T.,Jiang, Y.,Xu, H.E.,Yang, D.H.,Wang, M.W. (deposition date: 2021-12-16, release date: 2022-05-18, Last modification date: 2024-11-13)

Primary citation

Xu, Y.,Feng, W.,Zhou, Q.,Liang, A.,Li, J.,Dai, A.,Zhao, F.,Yan, J.,Chen, C.W.,Li, H.,Zhao, L.H.,Xia, T.,Jiang, Y.,Xu, H.E.,Yang, D.,Wang, M.W.
A distinctive ligand recognition mechanism by the human vasoactive intestinal polypeptide receptor 2.
Nat Commun, 13:2272-2272, 2022

PubMed Abstract: Class B1 of G protein-coupled receptors (GPCRs) comprises 15 members activated by physiologically important peptide hormones. Among them, vasoactive intestinal polypeptide receptor 2 (VIP2R) is expressed in the central and peripheral nervous systems and involved in a number of pathophysiological conditions, including pulmonary arterial hypertension, autoimmune and psychiatric disorders, in which it is thus a valuable drug target. Here, we report the cryo-electron microscopy structure of the human VIP2R bound to its endogenous ligand PACAP27 and the stimulatory G protein. Different from all reported peptide-bound class B1 GPCR structures, the N-terminal α-helix of VIP2R adopts a unique conformation that deeply inserts into a cleft between PACAP27 and the extracellular loop 1, thereby stabilizing the peptide-receptor interface. Its truncation or extension significantly decreased VIP2R-mediated cAMP accumulation. Our results provide additional information on peptide recognition and receptor activation among class B1 GPCRs and may facilitate the design of better therapeutics.

PubMed: 35477937
DOI: 10.1038/s41467-022-30041-z

Experimental method

ELECTRON MICROSCOPY (3.42 Å)