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Nat Struct Mol Biol. 2018 May;25(5):405-415. doi: 10.1038/s41594-018-0059-z. Epub 2018 Apr 30.

Conformational plasticity in the selectivity filter of the TRPV2 ion channel.

Author information

1
Department of Biochemistry, Duke University School of Medicine, Durham, NC, USA.
2
Department of Neurobiology, Duke University School of Medicine, Durham, NC, USA.
3
Department of Biochemistry, Duke University School of Medicine, Durham, NC, USA. seok-yong.lee@duke.edu.

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 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. Combined with functional characterizations, our studies reveal a structural basis for permeation of Ca2+ and large organic cations in TRPV2.

PMID:
29728656
PMCID:
PMC6025827
DOI:
10.1038/s41594-018-0059-z
[Indexed for MEDLINE]
Free PMC Article

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