3J9P

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

Summary for 3J9P

• Entry DOI: 10.2210/pdb3j9p/pdb
• EMDB information: 6267
• Descriptor: Maltose-binding periplasmic protein, Transient receptor potential cation channel subfamily A member 1 chimera (1 entity in total)
• Functional Keywords: trpa1, trp, transient, potential, receptor, ion channel, membrane protein, transport protein
• Biological source: Escherichia coli, Homo sapiens (bacteria, human)
• Total number of polymer chains: 4
• Total formula weight: 690302.25

Authors

Paulsen, C.E.,Armache, J.-P.,Gao, Y.,Cheng, Y.,Julius, D. (deposition date: 2015-02-14, release date: 2015-04-08, Last modification date: 2024-05-15)

Primary citation

Paulsen, C.E.,Armache, J.-P.,Gao, Y.,Cheng, Y.,Julius, D.
Structure of the TRPA1 ion channel suggests regulatory mechanisms.
Nature, 520:511-517, 2015

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.

PubMed: 25855297
DOI: 10.1038/nature14367

Experimental method

ELECTRON MICROSCOPY (4.24 Å)