3J9P

Structure of the TRPA1 ion channel determined by electron cryo-microscopy


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 4.24 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Structure of the TRPA1 ion channel suggests regulatory mechanisms.

Paulsen, C.E.Armache, J.-P.Gao, Y.Cheng, Y.Julius, D.

(2015) Nature 520: 511-517

  • DOI: https://doi.org/10.1038/nature14367
  • Primary Citation of Related Structures:  
    3J9P

  • PubMed Abstract: 

    The TRPA1 ion channel (also known as the wasabi receptor) is a detector of noxious chemical agents encountered in our environment or produced endogenously during tissue injury or drug metabolism. These include a broad class of electrophiles that activate the channel through covalent protein modification. TRPA1 antagonists hold potential for treating neurogenic inflammatory conditions provoked or exacerbated by irritant exposure. Despite compelling reasons to understand TRPA1 function, structural mechanisms underlying channel regulation remain obscure. Here we use single-particle electron cryo- microscopy to determine the structure of full-length human TRPA1 to ∼4 Å resolution in the presence of pharmacophores, including a potent antagonist. Several unexpected features are revealed, including an extensive coiled-coil assembly domain stabilized by polyphosphate co-factors and a highly integrated nexus that converges on an unpredicted transient receptor potential (TRP)-like allosteric domain. These findings provide new insights into the mechanisms of TRPA1 regulation, and establish a blueprint for structure-based design of analgesic and anti-inflammatory agents.


  • Organizational Affiliation

    Department of Physiology, University of California, San Francisco, California 94158-2517, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Maltose-binding periplasmic protein, Transient receptor potential cation channel subfamily A member 1 chimeraA [auth D],
B [auth A],
C [auth B],
D [auth C]
1,528Escherichia coliHomo sapiens
This entity is chimeric
Mutation(s): 0 
Gene Names: malEANKTM1
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P0AEX9 (Escherichia coli (strain K12))
Explore P0AEX9 
Go to UniProtKB:  P0AEX9
Find proteins for O75762 (Homo sapiens)
Explore O75762 
Go to UniProtKB:  O75762
PHAROS:  O75762
GTEx:  ENSG00000104321 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupsP0AEX9O75762
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 4.24 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
RECONSTRUCTIONRELION

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-04-08
    Type: Initial release
  • Version 1.1: 2015-04-22
    Changes: Database references
  • Version 1.2: 2015-04-29
    Changes: Database references
  • Version 1.3: 2018-07-18
    Changes: Data collection
  • Version 1.4: 2023-02-01
    Changes: Database references
  • Version 1.5: 2024-05-15
    Changes: Data collection