EMD-21249
Cryo-EM structure of an activated VIP1 receptor-G protein complex
EMD-21249
Single-particle3.2 Å
Deposition: 29/01/2020Map released: 02/09/2020
Last modified: 23/10/2024
Sample Organism:
Homo sapiens,
synthetic construct
Sample: PACAP27-VIP1R-Gs protein complex stabilized by Nanobody 35 and NanoBiT system
Fitted models: 6vn7 (Avg. Q-score: 0.427)
Deposition Authors: Duan J, Shen D-D
Sample: PACAP27-VIP1R-Gs protein complex stabilized by Nanobody 35 and NanoBiT system
Fitted models: 6vn7 (Avg. Q-score: 0.427)
Deposition Authors: Duan J, Shen D-D
Cryo-EM structure of an activated VIP1 receptor-G protein complex revealed by a NanoBiT tethering strategy.
Duan J,
Shen DD,
Zhou XE,
Bi P 
,
Liu QF,
Tan YX,
Zhuang YW ,
Zhang HB,
Xu PY,
Huang SJ ,
Ma SS,
He XH ,
Melcher K ,
Zhang Y ,
Xu HE ,
Jiang Y
(2020) Nat Commun , 11 , 4121 - 4121
,
Liu QF,
Tan YX,
Zhuang YW ,
Zhang HB,
Xu PY,
Huang SJ ,
Ma SS,
He XH ,
Melcher K ,
Zhang Y ,
Xu HE ,
Jiang Y
(2020) Nat Commun , 11 , 4121 - 4121
Abstract:
Vasoactive intestinal polypeptide receptor (VIP1R) is a widely expressed class B G protein-coupled receptor and a drug target for the treatment of neuronal, metabolic, and inflammatory diseases. However, our understanding of its mechanism of action and the potential of drug discovery targeting this receptor is limited by the lack of structural information of VIP1R. Here we report a cryo-electron microscopy structure of human VIP1R bound to PACAP27 and Gs heterotrimer, whose complex assembly is stabilized by a NanoBiT tethering strategy. Comparison with other class B GPCR structures reveals that PACAP27 engages VIP1R with its N-terminus inserting into the ligand binding pocket at the transmembrane bundle of the receptor, which subsequently couples to the G protein in a receptor-specific manner. This structure has provided insights into the molecular basis of PACAP27 binding and VIP receptor activation. The methodology of the NanoBiT tethering may help to provide structural information of unstable complexes.
Vasoactive intestinal polypeptide receptor (VIP1R) is a widely expressed class B G protein-coupled receptor and a drug target for the treatment of neuronal, metabolic, and inflammatory diseases. However, our understanding of its mechanism of action and the potential of drug discovery targeting this receptor is limited by the lack of structural information of VIP1R. Here we report a cryo-electron microscopy structure of human VIP1R bound to PACAP27 and Gs heterotrimer, whose complex assembly is stabilized by a NanoBiT tethering strategy. Comparison with other class B GPCR structures reveals that PACAP27 engages VIP1R with its N-terminus inserting into the ligand binding pocket at the transmembrane bundle of the receptor, which subsequently couples to the G protein in a receptor-specific manner. This structure has provided insights into the molecular basis of PACAP27 binding and VIP receptor activation. The methodology of the NanoBiT tethering may help to provide structural information of unstable complexes.