期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 116, 期 18, 页码 8869-8878出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1820323116
关键词
TRP channel; calcium; calmodulin; cryo-EM
资金
- European Union [748058]
- Netherlands Organisation for Health Research and Development [451001 004]
- Human Frontier Science Program Postdoctoral Fellowship
- Dutch Kidney Foundation student abroad fellowship
- Nora Baart Foundation of the Netherlands Foundation for the Advancement of Biochemistry
- National Institutes of Health [R01 GM098672, S10 OD020054, S10 OD021741, R35 NS105038]
- Marie Curie Actions (MSCA) [748058] Funding Source: Marie Curie Actions (MSCA)
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.
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