2NYJ

Crystal structure of the ankyrin repeat domain of TRPV1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.20 Å
  • R-Value Free: 0.286 
  • R-Value Work: 0.235 
  • R-Value Observed: 0.240 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

The Ankyrin Repeats of TRPV1 Bind Multiple Ligands and Modulate Channel Sensitivity.

Lishko, P.V.Procko, E.Jin, X.Phelps, C.B.Gaudet, R.

(2007) Neuron 54: 905-918

  • DOI: https://doi.org/10.1016/j.neuron.2007.05.027
  • Primary Citation of Related Structures:  
    2NYJ, 2PNN

  • PubMed Abstract: 

    TRPV1 plays a key role in nociception, as it is activated by heat, low pH, and ligands such as capsaicin, leading to a burning pain sensation. We describe the structure of the cytosolic ankyrin repeat domain (ARD) of TRPV1 and identify a multiligand-binding site important in regulating channel sensitivity within the TRPV1-ARD. The structure reveals a binding site that accommodates triphosphate nucleotides such as ATP, and biochemical studies demonstrate that calmodulin binds the same site. Electrophysiology experiments show that either ATP or PIP2 prevent desensitization to repeated applications of capsaicin, i.e., tachyphylaxis, while calmodulin plays an opposing role and is necessary for tachyphylaxis. Mutations in the TRPV1-ARD binding site eliminate tachyphylaxis. We present a model for the calcium-dependent regulation of TRPV1 via competitive interactions of ATP and calmodulin at the TRPV1-ARD-binding site and discuss its relationship to the C-terminal region previously implicated in interactions with PIP2 and calmodulin.


  • Organizational Affiliation

    Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, 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 1273Rattus norvegicusMutation(s): 0 
Gene Names: Trpv1Vr1Vr1l
UniProt
Find proteins for O35433 (Rattus norvegicus)
Explore O35433 
Go to UniProtKB:  O35433
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO35433
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ATP
Query on ATP

Download Ideal Coordinates CCD File 
B [auth A]ADENOSINE-5'-TRIPHOSPHATE
C10 H16 N5 O13 P3
ZKHQWZAMYRWXGA-KQYNXXCUSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
MSE
Query on MSE
A
L-PEPTIDE LINKINGC5 H11 N O2 SeMET
Experimental Data & Validation

Experimental Data

Unit Cell:
Length ( Å )Angle ( ˚ )
a = 124.721α = 90
b = 124.721β = 90
c = 62.767γ = 120
Software Package:
Software NamePurpose
SOLVEphasing
REFMACrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-07-03
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-18
    Changes: Refinement description
  • Version 1.4: 2023-12-27
    Changes: Data collection, Database references, Derived calculations