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

Byung-Il Yeh; Yung Kyu Kim; Wasey Jabbar; Chou-Long Huang

doi:10.1038/sj.emboj.7600795

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

Journal article

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

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

The EMBO journal, Vol.24(18), pp.3224-3234

09/21/2005

DOI: 10.1038/sj.emboj.7600795

PMCID: PMC1224685

PMID: 16121193

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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. ©2005 European Molecular Biology Organization.

substituted cysteine-accessibility method

transepithelial Ca2+ transport

transient receptor potential

Details

Title: Subtitle: Conformational changes of pore helix coupled to gating of TRPV5 by protons
Creators: Byung-Il Yeh - The University of Texas Southwestern Medical Center
Yung Kyu Kim - The University of Texas Southwestern Medical Center
Wasey Jabbar - The University of Texas Southwestern Medical Center
Chou-Long Huang - The University of Texas Southwestern Medical Center
Resource Type: Journal article
Publication Details: The EMBO journal, Vol.24(18), pp.3224-3234
DOI: 10.1038/sj.emboj.7600795
PMID: 16121193
PMCID: PMC1224685
NLM abbreviation: EMBO J
ISSN: 0261-4189
eISSN: 1460-2075
Publisher: John Wiley & Sons, Ltd
Number of pages: 11
Language: English
Date published: 09/21/2005
Academic Unit: Nephrology; Internal Medicine
Record Identifier: 9984359854202771

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