Gating of the TrkH ion channel by its associated RCK protein TrkA

Nature. 2013 Apr 18;496(7445):317-22. doi: 10.1038/nature12056.


TrkH belongs to a superfamily of K(+) transport proteins required for growth of bacteria in low external K(+) concentrations. The crystal structure of TrkH from Vibrio parahaemolyticus showed that TrkH resembles a K(+) channel and may have a gating mechanism substantially different from K(+) channels. TrkH assembles with TrkA, a cytosolic protein comprising two RCK (regulate the conductance of K(+)) domains, which are found in certain K(+) channels and control their gating. However, fundamental questions on whether TrkH is an ion channel and how it is regulated by TrkA remain unresolved. Here we show single-channel activity of TrkH that is upregulated by ATP via TrkA. We report two structures of the tetrameric TrkA ring, one in complex with TrkH and one in isolation, in which the ring assumes two markedly different conformations. These results suggest a mechanism for how ATP increases TrkH activity by inducing conformational changes in TrkA.

Publication types

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

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Adenosine Triphosphate / metabolism
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism*
  • Crystallography, X-Ray
  • Electric Conductivity
  • Ion Channel Gating*
  • Ion Transport
  • Models, Molecular
  • Protein Folding
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Vibrio parahaemolyticus


  • Bacterial Proteins
  • Adenosine Diphosphate
  • Adenosine Triphosphate