Structure of the TRPV1 Ion Channel Determined by Electron Cryo-Microscopy

Nature. 2013 Dec 5;504(7478):107-12. doi: 10.1038/nature12822.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Ankyrin Repeat
  • Cryoelectron Microscopy*
  • HEK293 Cells
  • Humans
  • Models, Molecular*
  • Protein Structure, Tertiary
  • Rats
  • TRPV Cation Channels / chemistry*

Substances

  • TRPV Cation Channels
  • Trpv1 protein, rat

Associated data

  • PDB/3J5P