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PDBsum entry 3j9p
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Transport protein
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PDB id
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3j9p
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References listed in PDB file
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Key reference
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Title
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Structure of the trpa1 ion channel suggests regulatory mechanisms.
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Authors
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C.E.Paulsen,
J.P.Armache,
Y.Gao,
Y.Cheng,
D.Julius.
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Ref.
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Nature, 2015,
520,
511-517.
[DOI no: ]
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PubMed id
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Abstract
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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.
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