Divalent cations activate TRPV1 through promoting conformational change of the extracellular region

Yang, Fan, Ma, Linlin, Cao, Xu, Wang, KeWei and Zheng, Jie (2014) Divalent cations activate TRPV1 through promoting conformational change of the extracellular region. Journal of General Physiology, 143 1: 91-103. doi:10.1085/jgp.201311024

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Author Yang, Fan
Ma, Linlin
Cao, Xu
Wang, KeWei
Zheng, Jie
Title Divalent cations activate TRPV1 through promoting conformational change of the extracellular region
Journal name Journal of General Physiology   Check publisher's open access policy
ISSN 0022-1295
1540-7748
Publication date 2014-01
Year available 2013
Sub-type Article (original research)
DOI 10.1085/jgp.201311024
Open Access Status File (Publisher version)
Volume 143
Issue 1
Start page 91
End page 103
Total pages 13
Place of publication New York, United States
Publisher Rockefeller University Press
Collection year 2014
Language eng
Formatted abstract
Divalent cations Mg2+ and Ba2+ selectively and directly potentiate transient receptor potential vanilloid type 1 heat activation by lowering the activation threshold into the room temperature range. We found that Mg2+ potentiates channel activation only from the extracellular side; on the intracellular side, Mg2+ inhibits channel current. By dividing the extracellularly accessible region of the channel protein into small segments and perturbing the structure of each segment with sequence replacement mutations, we observed that the S1-S2 linker, the S3-S4 linker, and the pore turret are all required for Mg2+ potentiation. Sequence replacements at these regions substantially reduced or eliminated Mg2+-induced activation at room temperature while sparing capsaicin activation. Heat activation was affected by many, but not all, of these structural alternations. These observations indicate that extracellular linkers and the turret may interact with each other. Site-directed fluorescence resonance energy transfer measurements further revealed that, like heat, Mg2+ also induces structural changes in the pore turret. Interestingly, turret movement induced by Mg2+ precedes channel activation, suggesting that Mg2+-induced conformational change in the extracellular region most likely serves as the cause of channel activation instead of a coincidental or accommodating structural adjustment.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
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