Conformational plasticity in the selectivity filter of the TRPV2 ion channel

Zubcevic, Lejla; Le, Son; Yang, Huanghe; Lee, Seok-Yong

doi:10.1038/s41594-018-0059-z

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

Journal Article · Mon Apr 30 00:00:00 EDT 2018 · Nature Structural & Molecular Biology

DOI:https://doi.org/10.1038/s41594-018-0059-z· OSTI ID:1438842

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Duke Univ. School of Medicine, Durham, NC (United States)

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.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE; National Institutes of Health (NIH)

Grant/Contract Number:: W-31-109-Eng-38; NIH R35 NS097241; NIH R00 NS086916; NIH DP2 GM126898; P41GM103403; S10 RR029205

OSTI ID:: 1438842

Journal Information:: Nature Structural & Molecular Biology, Vol. 25, Issue 5; ISSN 1545-9993

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 54 works

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

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