Structure of the human TRPM4 ion channel in a lipid nanodisc.
Article Details
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Autzen HE, Myasnikov AG, Campbell MG, Asarnow D, Julius D, Cheng Y
Structure of the human TRPM4 ion channel in a lipid nanodisc.
Science. 2018 Jan 12;359(6372):228-232. doi: 10.1126/science.aar4510. Epub 2017 Dec 7.
- PubMed ID
- 29217581 [ View in PubMed]
- Abstract
Transient receptor potential (TRP) melastatin 4 (TRPM4) is a widely expressed cation channel associated with a variety of cardiovascular disorders. TRPM4 is activated by increased intracellular calcium in a voltage-dependent manner but, unlike many other TRP channels, is permeable to monovalent cations only. Here we present two structures of full-length human TRPM4 embedded in lipid nanodiscs at ~3-angstrom resolution, as determined by single-particle cryo-electron microscopy. These structures, with and without calcium bound, reveal a general architecture for this major subfamily of TRP channels and a well-defined calcium-binding site within the intracellular side of the S1-S4 domain. The structures correspond to two distinct closed states. Calcium binding induces conformational changes that likely prime the channel for voltage-dependent opening.