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PMID: 24305160 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Structure of the TRPV1 ion channel determined by electron cryo-microscopy.

Nature ·Vol. 504 ·No. 7478 ·2013-12-05 ·Pages 107-12

Liao M, Cao E, Julius D, Cheng Y

Abstract

Transient receptor potential (TRP) channels are sensors for a wide range of cellular and environmental signals, but elucidating how these channels respond to physical and chemical stimuli has been hampered by a lack of detailed structural information. Here we exploit advances in electron cryo-microscopy to determine the structure of a mammalian TRP channel, TRPV1, at 3.4 Å resolution, breaking the side-chain resolution barrier for membrane proteins without crystallization. Like voltage-gated channels, TRPV1 exhibits four-fold symmetry around a central ion pathway formed by transmembrane segments 5-6 (S5-S6) and the intervening pore loop, which is flanked by S1-S4 voltage-sensor-like domains. TRPV1 has a wide extracellular 'mouth' with a short selectivity filter. The conserved 'TRP domain' interacts with the S4-S5 linker, consistent with its contribution to allosteric modulation. Subunit organization is facilitated by interactions among cytoplasmic domains, including amino-terminal ankyrin repeats. These observations provide a structural blueprint for understanding unique aspects of TRP channel function.

MeSH Terms
Animals Ankyrin Repeat Cryoelectron Microscopy HEK293 Cells Humans Models, Molecular Protein Structure, Tertiary Rats TRPV Cation Channels/chemistry
Chemicals
TRPV Cation Channels Trpv1 protein, rat
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Liao Maofu
1] Keck Advanced Microscopy Laboratory, Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158-2517, USA [2].
Cao Erhu
Julius David
Cheng Yifan
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Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
DOI
10.1038/nature12822
Published
2013-12-05
Pages
107-12
Language
English
Region
England
NLM ID
0410462
PMCID
PMC4078027
Subset
IM
Grants
NINDS NIH HHS · R01NS047723 · United States
NINDS NIH HHS · R01 NS047723 · United States
NINDS NIH HHS · R01 NS065071 · United States
NINDS NIH HHS · R01NS065071 · United States
NIGMS NIH HHS · R01 GM098672 · United States
NCRR NIH HHS · S10RR026814 · United States
NIGMS NIH HHS · R01GM098672 · United States
NCRR NIH HHS · S10 RR026814 · United States
Databases
PDB
3J5P
Corrections
CommentIn
PMID: 24305155
External Links
PubMed source DOI: 10.1038/nature12822 PMC Full Text View journal details
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