6BBJ

Xenopus Tropicalis TRPV4

  • Classification: METAL TRANSPORT
  • Organism(s): Xenopus tropicalis
  • Expression System: Pichia
  • Mutation(s): No 

  • Deposited: 2017-10-18 Released: 2018-02-28 
  • Deposition Author(s): Deng, Z., Hite, R.K., Yuan, P.
  • Funding Organization(s): National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS), National Institutes of Health/National Cancer Institute (NIH/NCI), American Heart Association

Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.80 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Cryo-EM and X-ray structures of TRPV4 reveal insight into ion permeation and gating mechanisms.

Deng, Z.Paknejad, N.Maksaev, G.Sala-Rabanal, M.Nichols, C.G.Hite, R.K.Yuan, P.

(2018) Nat Struct Mol Biol 25: 252-260

  • DOI: https://doi.org/10.1038/s41594-018-0037-5
  • Primary Citation of Related Structures:  
    6BBJ, 6C8F, 6C8G, 6C8H

  • PubMed Abstract: 

    The transient receptor potential (TRP) channel TRPV4 participates in multiple biological processes, and numerous TRPV4 mutations underlie several distinct and devastating diseases. Here we present the cryo-EM structure of Xenopus tropicalis TRPV4 at 3.8-Å resolution. The ion-conduction pore contains an intracellular gate formed by the inner helices, but lacks any extracellular gate in the selectivity filter, as observed in other TRPV channels. Anomalous X-ray diffraction analyses identify a single ion-binding site in the selectivity filter, thus explaining TRPV4 nonselectivity. Structural comparisons with other TRP channels and distantly related voltage-gated cation channels reveal an unprecedented, unique packing interface between the voltage-sensor-like domain and the pore domain, suggesting distinct gating mechanisms. Moreover, our structure begins to provide mechanistic insights to the large set of pathogenic mutations, offering potential opportunities for drug development.


  • Organizational Affiliation

    Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Transient receptor potential cation channel, subfamily V, member 4
A, B, C, D
868Xenopus tropicalisMutation(s): 0 
Gene Names: trpv4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.80 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
MODEL REFINEMENTPHENIX1.12-2829
MODEL REFINEMENTREFMAC5.8.0158
RECONSTRUCTIONFREALIGN9.11

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)United StatesR01NS099341-01A1
National Institutes of Health/National Cancer Institute (NIH/NCI)United StatesP30 CA008748
American Heart AssociationUnited States17SDG33400229

Revision History  (Full details and data files)

  • Version 1.0: 2018-02-28
    Type: Initial release
  • Version 1.1: 2018-03-14
    Changes: Author supporting evidence, Database references
  • Version 1.2: 2019-12-04
    Changes: Author supporting evidence
  • Version 1.3: 2024-03-13
    Changes: Data collection, Database references