4.8 Article

Structural insight into TRPV5 channel function and modulation

出版社

NATL ACAD SCIENCES
DOI: 10.1073/pnas.1820323116

关键词

TRP channel; calcium; calmodulin; cryo-EM

资金

  1. European Union [748058]
  2. Netherlands Organisation for Health Research and Development [451001 004]
  3. Human Frontier Science Program Postdoctoral Fellowship
  4. Dutch Kidney Foundation student abroad fellowship
  5. Nora Baart Foundation of the Netherlands Foundation for the Advancement of Biochemistry
  6. National Institutes of Health [R01 GM098672, S10 OD020054, S10 OD021741, R35 NS105038]
  7. Marie Curie Actions (MSCA) [748058] Funding Source: Marie Curie Actions (MSCA)

向作者/读者索取更多资源

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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