7vqx

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

spinqualitylabelsall models 7vqx, resolution 2.74Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7vqx is a 6 chain structure with sequence from Bos taurus, Homo sapiens, Rattus norvegicus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.74Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GNAS2_BOVIN Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(s) protein is involved in hormonal regulation of adenylate cyclase: it activates the cyclase in response to beta-adrenergic stimuli. Publication Abstract from PubMed 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 alpha-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. A distinctive ligand recognition mechanism by the human vasoactive intestinal polypeptide receptor 2.,Xu Y, Feng W, Zhou Q, Liang A, Li J, Dai A, Zhao F, Yan J, Chen CW, Li H, Zhao LH, Xia T, Jiang Y, Xu HE, Yang D, Wang MW Nat Commun. 2022 Apr 27;13(1):2272. doi: 10.1038/s41467-022-30041-z. PMID:35477937 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Transducin 3D structures

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