4DX1

Crystal structure of the human TRPV4 ankyrin repeat domain


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.85 Å
  • R-Value Free: 0.279 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.218 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural and biochemical consequences of disease-causing mutations in the ankyrin repeat domain of the human TRPV4 channel.

Inada, H.Procko, E.Sotomayor, M.Gaudet, R.

(2012) Biochemistry 51: 6195-6206

  • DOI: https://doi.org/10.1021/bi300279b
  • Primary Citation of Related Structures:  
    4DX1, 4DX2

  • PubMed Abstract: 

    The TRPV4 calcium-permeable cation channel plays important physiological roles in osmosensation, mechanosensation, cell barrier formation, and bone homeostasis. Recent studies reported that mutations in TRPV4, including some in its ankyrin repeat domain (ARD), are associated with human inherited diseases, including neuropathies and skeletal dysplasias, probably because of the increased constitutive activity of the channel. TRPV4 activity is regulated by the binding of calmodulin and small molecules such as ATP to the ARD at its cytoplasmic N-terminus. We determined structures of ATP-free and -bound forms of human TRPV4-ARD and compared them with available TRPV-ARD structures. The third inter-repeat loop region (Finger 3 loop) is flexible and may act as a switch to regulate channel activity. Comparisons of TRPV-ARD structures also suggest an evolutionary link between ARD structure and ATP binding ability. Thermal stability analyses and molecular dynamics simulations suggest that ATP increases stability in TRPV-ARDs that can bind ATP. Biochemical analyses of a large panel of TRPV4-ARD mutations associated with human inherited diseases showed that some impaired thermal stability while others weakened ATP binding ability, suggesting molecular mechanisms for the diseases.


  • Organizational Affiliation

    Department of Molecular and Cellular Biology, Harvard University, 52 Oxford Street, Cambridge, MA 02138, 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
259Homo sapiensMutation(s): 0 
Gene Names: TRPV4VRL2VROAC
UniProt & NIH Common Fund Data Resources
Find proteins for Q9HBA0 (Homo sapiens)
Explore Q9HBA0 
Go to UniProtKB:  Q9HBA0
PHAROS:  Q9HBA0
GTEx:  ENSG00000111199 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9HBA0
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.85 Å
  • R-Value Free: 0.279 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.218 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.37α = 90
b = 53.37β = 90
c = 440.711γ = 120
Software Package:
Software NamePurpose
SCALEPACKdata scaling
MOLREPphasing
REFMACrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-07-18
    Type: Initial release
  • Version 1.1: 2012-12-19
    Changes: Database references
  • Version 1.2: 2024-02-28
    Changes: Data collection, Database references, Derived calculations