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Literature DB >> 30975749

Structural insight into TRPV5 channel function and modulation.

Shangyu Dang¹, Mark K van Goor^1,2, Daniel Asarnow¹, YongQiang Wang³, David Julius⁴, Yifan Cheng^5,3, Jenny van der Wijst^5,2.

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.

Entities: Chemical Gene

Keywords: TRP channel; calcium; calmodulin; cryo-EM

Year: 2019 PMID： 30975749 PMCID： PMC6500171 DOI： 10.1073/pnas.1820323116

Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205

48 in total

Structural insight into TRPV5 channel function and modulation.

1. Whole-cell and single channel monovalent cation currents through the novel rabbit epithelial Ca2+ channel ECaC.

2. Modulation of the epithelial calcium channel, ECaC, by intracellular Ca2+.

3. The carboxyl terminus of the epithelial Ca(2+) channel ECaC1 is involved in Ca(2+)-dependent inactivation.

4. UCSF Chimera--a visualization system for exploratory research and analysis.

Review 5. Multiple roles of calmodulin and other Ca(2+)-binding proteins in the functional regulation of TRP channels.

6. Permeation and gating properties of the novel epithelial Ca(2+) channel.

7. The single pore residue Asp542 determines Ca2+ permeation and Mg2+ block of the epithelial Ca2+ channel.

8. Regulation of the mouse epithelial Ca2(+) channel TRPV6 by the Ca(2+)-sensor calmodulin.

9. Calmodulin is essential for cardiac IKS channel gating and assembly: impaired function in long-QT mutations.

10. Negative Staining and Image Classification - Powerful Tools in Modern Electron Microscopy.

Review 1. Structural insights into the gating mechanisms of TRPV channels.

2. Ca_V channels reject signaling from a second CaM in eliciting Ca²⁺-dependent feedback regulation.

Review 3. Structure and function of the calcium-selective TRP channel TRPV6.

Review 4. Calcium selective channel TRPV6: Structure, function, and implications in health and disease.

5. Interfacial Binding Sites for Cholesterol on TRP Ion Channels.

6. Structural Basis for High-Affinity Trapping of the Na_V1.7 Channel in Its Resting State by Tarantula Toxin.

7. Structure and mechanism of the mitochondrial Ca²⁺ uniporter holocomplex.

Review 8. Drug discovery in the era of cryo-electron microscopy.

9. Stable Picodisc Assemblies from Saposin Proteins and Branched Detergents.

Review 10. Assessing the Role of Lipids in the Molecular Mechanism of Membrane Proteins.