National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM098672
米国
National Institutes of Health/Office of the Director
S10OD020054
米国
National Institutes of Health/Office of the Director
S10OD021741
米国
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
R01NS047723
米国
Danish Council of Independent Research
DFF-5051-00085
デンマーク
引用
ジャーナル: Science / 年: 2018 タイトル: Structure of the human TRPM4 ion channel in a lipid nanodisc. 著者: Henriette E Autzen / Alexander G Myasnikov / Melody G Campbell / Daniel Asarnow / David Julius / Yifan Cheng / 要旨: 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 ...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.
EMPIAR-10127 (タイトル: Human TRPM4 ion channel in a lipid nanodisc in a calcium-bound state Data size: 84.4 Data #1: particle stacks of TRPM4 particles post 2D clean-up [picked particles - multiframe - processed])
Sharpened map of human TRPM4 ion channel in lipid nanodisc with 5 mM CaCl2. This reconstruction is focused on transmembrane domain, central coiled-coil domain, and MHR4 domain. C4 symmetry is applied.
Sharpened map of human TRPM4 ion channel in lipid nanodisc with 5 mM CaCl2. This reconstruction is focused on monomeric soluble domain without symmetry.