Structural determinants of gating in the TRPV1 channel

Nat Struct Mol Biol. 2009 Jul;16(7):704-10. doi: 10.1038/nsmb.1633. Epub 2009 Jun 28.


Transient receptor potential vanilloid 1 (TRPV1) channels mediate several types of physiological responses. Despite the importance of these channels in pain detection and inflammation, little is known about how their structural components convert different types of stimuli into channel activity. To localize the activation gate of these channels, we inserted cysteines along the S6 segment of mutant TRPV1 channels and assessed their accessibility to thiol-modifying agents. We show that access to the pore of TRPV1 is gated by S6 in response to both capsaicin binding and increases in temperature, that the pore-forming S6 segments are helical structures and that two constrictions are present in the pore: one that impedes the access of large molecules and the other that hampers the access of smaller ions and constitutes an activation gate of these channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Capsaicin / metabolism
  • Cysteine / chemistry
  • Ion Channel Gating / physiology
  • Ions / metabolism
  • Leucine / chemistry
  • Mesylates / chemistry
  • Models, Molecular*
  • Molecular Sequence Data
  • Protein Structure, Secondary*
  • Protein Structure, Tertiary*
  • Rats
  • Sensory System Agents / metabolism
  • TRPV Cation Channels / chemistry*
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism*
  • Temperature
  • Tyrosine / chemistry


  • Ions
  • Mesylates
  • Sensory System Agents
  • TRPV Cation Channels
  • Trpv1 protein, rat
  • Tyrosine
  • Leucine
  • Cysteine
  • Capsaicin