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TitleA distinctive ligand recognition mechanism by the human vasoactive intestinal polypeptide receptor 2.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 2272, Year 2022
Publish dateApr 27, 2022
AuthorsYingna 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 AbstractClass 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 linksNat Commun / PubMed:35477937 / PubMed Central
MethodsEM (single particle)
Resolution2.74 - 3.42 Å
Structure data

32095

7vqx

EMDB-32095, PDB-7vqx:
Cryo-EM structure of human vasoactive intestinal polypeptide receptor 2 (VIP2R) in complex with PACAP27 and Gs
Method: EM (single particle) / Resolution: 2.74 Å

32401

7wbj

EMDB-32401, PDB-7wbj:
Cryo-EM structure of N-terminal modified human vasoactive intestinal polypeptide receptor 2 (VIP2R) in complex with PACAP27 and Gs
Method: EM (single particle) / Resolution: 3.42 Å

Source
  • bos taurus (cattle)
  • homo sapiens (human)
  • synthetic construct (others)
  • rattus norvegicus (Norway rat)
KeywordsSTRUCTURAL PROTEIN / vasoactive intestinal polypeptide receptor 2 / G protein-coupled receptor / ligand recognition

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