Conformational changes of pore helix coupled to gating of TRPV5 by protons

Byung Il Yeh, Kyu Kim Yung, Wasey Jabbar, Chou Long Huang

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

The transient receptor potential channel TRPV5 constitutes the apical entry pathway for transepithelial Ca2+ transport. We showed that TRPV5 was inhibited by both physiological intra- and extracellular acid pH. Inhibition of TRPV5 by internal protons was enhanced by extracellular acidification. Similarly, inhibition by external protons was enhanced by intracellular acidification. Mutation of either an extra- or an intracellular pH sensor blunted the crossinhibition by internal and external protons. Both internal and external protons regulated the selectivity filter gate. Using the substituted cysteine accessibility method, we found that intracellular acidification of TRPV5 caused a conformational change of the pore helix consistent with clockwise rotation along its long axis. Thus, rotation of pore helix caused by internal protons facilitates closing of TRPV5 by external protons. This regulation by protons likely contributes to pathogenesis of disturbances of Ca2+ transport in many diseased states. Rotation of pore helix may be a common mechanism for crossregulation of ion channels by extra- and intracellular signals.

Original languageEnglish (US)
Pages (from-to)3224-3234
Number of pages11
JournalEMBO Journal
Volume24
Issue number18
DOIs
StatePublished - Sep 21 2005

Fingerprint

Protons
Acidification
pH sensors
Transient Receptor Potential Channels
Ion Channels
Cysteine
Mutation
Acids

Keywords

  • Substituted cysteine-accessibility method
  • Transepithelial Ca transport
  • Transient receptor potential

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Conformational changes of pore helix coupled to gating of TRPV5 by protons. / Yeh, Byung Il; Yung, Kyu Kim; Jabbar, Wasey; Huang, Chou Long.

In: EMBO Journal, Vol. 24, No. 18, 21.09.2005, p. 3224-3234.

Research output: Contribution to journalArticle

Yeh, Byung Il ; Yung, Kyu Kim ; Jabbar, Wasey ; Huang, Chou Long. / Conformational changes of pore helix coupled to gating of TRPV5 by protons. In: EMBO Journal. 2005 ; Vol. 24, No. 18. pp. 3224-3234.
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