PDBsum entry 3j9p

Transport protein

PDB id: 3j9p

Contents

Protein chains

560 a.a.

PDB id:

3j9p

Name:

Transport protein

Title:

Structure of the trpa1 ion channel determined by electron cryo- microscopy

Structure:

Maltose-binding periplasmic protein, transient receptor potential cation channel subfamily a member 1 chimera. Chain: d, a, b, c. Fragment: see remark 999. Synonym: ankyrin-like with transmembrane domains protein 1, transformation-sensitive protein p120, transient receptor potential ankyrin 1 ion channel. Engineered: yes

Source:

Escherichia coli, homo sapiens. Bacteria, human. Organism_taxid: 562, 9606. Gene: male, anktm1, trpa1. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293 gnti-

Authors:

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

Key ref:

C.E.Paulsen et al. (2015). Structure of the TRPA1 ion channel suggests regulatory mechanisms. Nature, 520, 511-517. PubMed id: 25855297 DOI: 10.1038/nature14367

Date:

14-Feb-15 Release date: 08-Apr-15

Protein chains

O75762  (TRPA1_HUMAN) -  Transient receptor potential cation channel subfamily A member 1 from Homo sapiens

Seq: 1119 a.a.

Struc: 560 a.a.*

Protein chains

P0AEX9  (MALE_ECOLI) -  Maltose/maltodextrin-binding periplasmic protein from Escherichia coli (strain K12)

Seq: 396 a.a.

Struc: 560 a.a.*

* PDB and UniProt seqs differ at 183 residue positions (black crosses)

DOI no: 10.1038/nature14367

Nature 520:511-517 (2015)

PubMed id: 25855297

Structure of the TRPA1 ion channel suggests regulatory mechanisms.

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

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.