Structural insight into TRPV5 channel function and modulation.


Journal

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876

Informations de publication

Date de publication:
30 04 2019
Historique:
pubmed: 13 4 2019
medline: 26 3 2020
entrez: 13 4 2019
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 30975749
pii: 1820323116
doi: 10.1073/pnas.1820323116
pmc: PMC6500171
doi:

Substances chimiques

Calcium Radioisotopes 0
TRPV Cation Channels 0
Calcium SY7Q814VUP

Banques de données

PDB
['6O1N', '6O1P', '6O1U', '6O20']

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

8869-8878

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM098672
Pays : United States
Organisme : NINDS NIH HHS
ID : R35 NS105038
Pays : United States
Organisme : NIH HHS
ID : S10 OD020054
Pays : United States
Organisme : NIH HHS
ID : S10 OD021741
Pays : United States

Déclaration de conflit d'intérêts

The authors declare no conflict of interest.

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Auteurs

Shangyu Dang (S)

Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143.

Mark K van Goor (MK)

Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143.
Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.

Daniel Asarnow (D)

Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143.

YongQiang Wang (Y)

Howard Hughes Medical Institute, University of California, San Francisco, CA 94143.

David Julius (D)

Department of Physiology, University of California, San Francisco, CA 94143 david.julius@ucsf.edu yifan.cheng@ucsf.edu jenny.vanderwijst@radboudumc.nl.

Yifan Cheng (Y)

Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143; david.julius@ucsf.edu yifan.cheng@ucsf.edu jenny.vanderwijst@radboudumc.nl.
Howard Hughes Medical Institute, University of California, San Francisco, CA 94143.

Jenny van der Wijst (J)

Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143; david.julius@ucsf.edu yifan.cheng@ucsf.edu jenny.vanderwijst@radboudumc.nl.
Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.

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