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Title | A distinctive ligand recognition mechanism by the human vasoactive intestinal polypeptide receptor 2. |
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Journal, issue, pages | Nat Commun, Vol. 13, Issue 1, Page 2272, Year 2022 |
Publish date | Apr 27, 2022 |
Authors | Yingna Xu / Wenbo Feng / Qingtong Zhou / Anyi Liang / Jie Li / Antao Dai / Fenghui Zhao / Jiahui Yan / Chuan-Wei Chen / Hao Li / Li-Hua Zhao / Tian Xia / Yi Jiang / H Eric Xu / Dehua Yang / Ming-Wei Wang / |
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 ...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. |
External links | Nat Commun / PubMed:35477937 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.74 - 3.42 Å |
Structure data | EMDB-32095, PDB-7vqx: EMDB-32401, PDB-7wbj: |
Source |
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Keywords | STRUCTURAL PROTEIN / vasoactive intestinal polypeptide receptor 2 / G protein-coupled receptor / ligand recognition |