6VN7

Cryo-EM structure of an activated VIP1 receptor-G protein complex


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.20 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


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Literature

Cryo-EM structure of an activated VIP1 receptor-G protein complex revealed by a NanoBiT tethering strategy.

Duan, J.Shen, D.D.Zhou, X.E.Bi, P.Liu, Q.F.Tan, Y.X.Zhuang, Y.W.Zhang, H.B.Xu, P.Y.Huang, S.J.Ma, S.S.He, X.H.Melcher, K.Zhang, Y.Xu, H.E.Jiang, Y.

(2020) Nat Commun 11: 4121-4121

  • DOI: https://doi.org/10.1038/s41467-020-17933-8
  • Primary Citation of Related Structures:  
    6VN7

  • PubMed 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.


  • Organizational Affiliation

    The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Vasoactive intestinal polypeptide receptor 1A [auth R]582Homo sapiensMutation(s): 0 
Gene Names: VIPR1
Membrane Entity: Yes 
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Find proteins for P32241 (Homo sapiens)
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Go to UniProtKB:  P32241
PHAROS:  P32241
GTEx:  ENSG00000114812 
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UniProt GroupP32241
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Pituitary adenylate cyclase-activating polypeptideB [auth L]27Homo sapiensMutation(s): 0 
Membrane Entity: Yes 
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Find proteins for P18509 (Homo sapiens)
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PHAROS:  P18509
GTEx:  ENSG00000141433 
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UniProt GroupP18509
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Guanine nucleotide-binding protein G(s) subunit alpha isoforms shortC [auth A]394Homo sapiensMutation(s): 0 
Gene Names: GNASGNAS1GSP
Membrane Entity: Yes 
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Find proteins for P63092 (Homo sapiens)
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PHAROS:  P63092
GTEx:  ENSG00000087460 
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UniProt GroupP63092
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1D [auth B]377Homo sapiensMutation(s): 0 
Gene Names: GNB1
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Find proteins for P62873 (Homo sapiens)
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PHAROS:  P62873
GTEx:  ENSG00000078369 
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UniProt GroupP62873
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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2E [auth G]71Homo sapiensMutation(s): 0 
Gene Names: GNG2
Membrane Entity: Yes 
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GTEx:  ENSG00000186469 
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UniProt GroupP59768
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Entity ID: 6
MoleculeChains Sequence LengthOrganismDetailsImage
Nanobody 35F [auth N]134synthetic constructMutation(s): 0 
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Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CLR
Query on CLR

Download Ideal Coordinates CCD File 
G [auth R]
H [auth R]
I [auth R]
J [auth R]
K [auth R]
G [auth R],
H [auth R],
I [auth R],
J [auth R],
K [auth R],
L [auth R]
CHOLESTEROL
C27 H46 O
HVYWMOMLDIMFJA-DPAQBDIFSA-N
PLM
Query on PLM

Download Ideal Coordinates CCD File 
M [auth R],
N [auth R],
O [auth R],
P [auth R]
PALMITIC ACID
C16 H32 O2
IPCSVZSSVZVIGE-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.20 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Natural Science Foundation of China (NSFC)China31770796
Ministry of Science and Technology (MoST, China)China2018YFA0507002

Revision History  (Full details and data files)

  • Version 1.0: 2020-09-02
    Type: Initial release