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Title: Conformational plasticity in the selectivity filter of the TRPV2 ion channel

Abstract

Transient receptor potential vanilloid (TRPV) channels are activated by ligands and heat and are involved in various physiological processes. In contrast to the architecturally related voltage-gated cation channels, TRPV1 and TRPV2 subtypes possess another activation gate at the selectivity filter that can open widely enough to permeate large organic cations. Despite recent structural advances, the mechanism of selectivity filter gating and permeation for both metal ions and large molecules by TRPV1 or TRPV2 is not well known. Here, we determined two crystal structures of rabbit TRPV2 in its Ca 2+-bound and resiniferatoxin (RTx)- and Ca 2+-bound forms, to 3.9 Å and 3.1 Å, respectively. Notably, our structures show that RTx binding leads to two-fold symmetric opening of the selectivity filter of TRPV2 that is wide enough for large organic cation permeation. Furthermore,combined with functional characterizations, our studies reveal a structural basis for permeation of Ca 2+ and large organic cations in TRPV2.

Authors:
ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [1]
  1. Duke Univ. School of Medicine, Durham, NC (United States)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE; National Institutes of Health (NIH)
OSTI Identifier:
1438842
Grant/Contract Number:  
W-31-109-Eng-38; NIH R35 NS097241; NIH R00 NS086916; NIH DP2 GM126898; P41GM103403; S10 RR029205
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Nature Structural & Molecular Biology
Additional Journal Information:
Journal Volume: 25; Journal Issue: 5; Journal ID: ISSN 1545-9993
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; Ion transport; Transient receptor potential channels; X-ray crystallography

Citation Formats

Zubcevic, Lejla, Le, Son, Yang, Huanghe, and Lee, Seok-Yong. Conformational plasticity in the selectivity filter of the TRPV2 ion channel. United States: N. p., 2018. Web. doi:10.1038/s41594-018-0059-z.
Zubcevic, Lejla, Le, Son, Yang, Huanghe, & Lee, Seok-Yong. Conformational plasticity in the selectivity filter of the TRPV2 ion channel. United States. doi:10.1038/s41594-018-0059-z.
Zubcevic, Lejla, Le, Son, Yang, Huanghe, and Lee, Seok-Yong. Mon . "Conformational plasticity in the selectivity filter of the TRPV2 ion channel". United States. doi:10.1038/s41594-018-0059-z. https://www.osti.gov/servlets/purl/1438842.
@article{osti_1438842,
title = {Conformational plasticity in the selectivity filter of the TRPV2 ion channel},
author = {Zubcevic, Lejla and Le, Son and Yang, Huanghe and Lee, Seok-Yong},
abstractNote = {Transient receptor potential vanilloid (TRPV) channels are activated by ligands and heat and are involved in various physiological processes. In contrast to the architecturally related voltage-gated cation channels, TRPV1 and TRPV2 subtypes possess another activation gate at the selectivity filter that can open widely enough to permeate large organic cations. Despite recent structural advances, the mechanism of selectivity filter gating and permeation for both metal ions and large molecules by TRPV1 or TRPV2 is not well known. Here, we determined two crystal structures of rabbit TRPV2 in its Ca2+-bound and resiniferatoxin (RTx)- and Ca2+-bound forms, to 3.9 Å and 3.1 Å, respectively. Notably, our structures show that RTx binding leads to two-fold symmetric opening of the selectivity filter of TRPV2 that is wide enough for large organic cation permeation. Furthermore,combined with functional characterizations, our studies reveal a structural basis for permeation of Ca2+ and large organic cations in TRPV2.},
doi = {10.1038/s41594-018-0059-z},
journal = {Nature Structural & Molecular Biology},
issn = {1545-9993},
number = 5,
volume = 25,
place = {United States},
year = {2018},
month = {4}
}

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Cited by: 23 works
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