Structural insight into TRPV5 channel function and modulation

Shangyu Dang; Mark K. Van Goor; Daniel Asarnow; Yong Qiang Wang; David Julius; Yifan Cheng; Jenny van der Wijst

doi:10.1073/pnas.1820323116

Structural insight into TRPV5 channel function and modulation

Shangyu Dang, Mark K. Van Goor, Daniel Asarnow, Yong Qiang Wang, David Julius^*, Yifan Cheng, Jenny van der Wijst

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

92 Citations (Scopus)

Abstract

TRPV5 (transient receptor potential vanilloid 5) is a unique calcium-selective TRP channel essential for calcium homeostasis. Unlike other TRPV channels, TRPV5 and its close homolog, TRPV6, do not exhibit thermosensitivity or ligand-dependent activation but are constitutively open at physiological membrane potentials and modulated by calmodulin (CaM) in a calcium-dependent manner. Here we report high-resolution electron cryomicroscopy structures of truncated and full-length TRPV5 in lipid nanodiscs, as well as of a TRPV5 W583A mutant and TRPV5 in complex with CaM. These structures highlight the mechanism of calcium regulation and reveal a flexible stoichiometry of CaM binding to TRPV5.

Original language	English
Pages (from-to)	8869-8878
Number of pages	10
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	116
Issue number	18
DOIs	https://doi.org/10.1073/pnas.1820323116
Publication status	Published - 30 Apr 2019
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2019 National Academy of Sciences. All rights reserved.

Keywords

Calcium
Calmodulin
Cryo-EM
TRP channel

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10.1073/pnas.1820323116

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title = "Structural insight into TRPV5 channel function and modulation",

abstract = "TRPV5 (transient receptor potential vanilloid 5) is a unique calcium-selective TRP channel essential for calcium homeostasis. Unlike other TRPV channels, TRPV5 and its close homolog, TRPV6, do not exhibit thermosensitivity or ligand-dependent activation but are constitutively open at physiological membrane potentials and modulated by calmodulin (CaM) in a calcium-dependent manner. Here we report high-resolution electron cryomicroscopy structures of truncated and full-length TRPV5 in lipid nanodiscs, as well as of a TRPV5 W583A mutant and TRPV5 in complex with CaM. These structures highlight the mechanism of calcium regulation and reveal a flexible stoichiometry of CaM binding to TRPV5.",

keywords = "Calcium, Calmodulin, Cryo-EM, TRP channel",

author = "Shangyu Dang and \{Van Goor\}, \{Mark K.\} and Daniel Asarnow and Wang, \{Yong Qiang\} and David Julius and Yifan Cheng and \{van der Wijst\}, Jenny",

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doi = "10.1073/pnas.1820323116",

language = "English",

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TY - JOUR

T1 - Structural insight into TRPV5 channel function and modulation

AU - Dang, Shangyu

AU - Van Goor, Mark K.

AU - Asarnow, Daniel

AU - Wang, Yong Qiang

AU - Julius, David

AU - Cheng, Yifan

AU - van der Wijst, Jenny

PY - 2019/4/30

Y1 - 2019/4/30

N2 - TRPV5 (transient receptor potential vanilloid 5) is a unique calcium-selective TRP channel essential for calcium homeostasis. Unlike other TRPV channels, TRPV5 and its close homolog, TRPV6, do not exhibit thermosensitivity or ligand-dependent activation but are constitutively open at physiological membrane potentials and modulated by calmodulin (CaM) in a calcium-dependent manner. Here we report high-resolution electron cryomicroscopy structures of truncated and full-length TRPV5 in lipid nanodiscs, as well as of a TRPV5 W583A mutant and TRPV5 in complex with CaM. These structures highlight the mechanism of calcium regulation and reveal a flexible stoichiometry of CaM binding to TRPV5.

AB - TRPV5 (transient receptor potential vanilloid 5) is a unique calcium-selective TRP channel essential for calcium homeostasis. Unlike other TRPV channels, TRPV5 and its close homolog, TRPV6, do not exhibit thermosensitivity or ligand-dependent activation but are constitutively open at physiological membrane potentials and modulated by calmodulin (CaM) in a calcium-dependent manner. Here we report high-resolution electron cryomicroscopy structures of truncated and full-length TRPV5 in lipid nanodiscs, as well as of a TRPV5 W583A mutant and TRPV5 in complex with CaM. These structures highlight the mechanism of calcium regulation and reveal a flexible stoichiometry of CaM binding to TRPV5.

KW - Calcium

KW - Calmodulin

KW - Cryo-EM

KW - TRP channel

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UR - https://www.scopus.com/pages/publications/85065509609

U2 - 10.1073/pnas.1820323116

DO - 10.1073/pnas.1820323116

M3 - Journal Article

C2 - 30975749

SN - 0027-8424

VL - 116

SP - 8869

EP - 8878

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 18

ER -

Structural insight into TRPV5 channel function and modulation

Abstract

Bibliographical note

Keywords

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