National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM098672
米国
National Institutes of Health/Office of the Director
S10OD021741
米国
National Institutes of Health/Office of the Director
S10OD020054
米国
Danish Council of Independent Research
DFF-5051-00085
デンマーク
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
R01NS047723
米国
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-10126 (タイトル: Human TRPM4 ion channel in a lipid nanodisc in a calcium-free state Data size: 162.5 Data #1: particle stacks of TRPM4 particles post 2D clean-up [picked particles - multiframe - processed])
Sharpened 3D density map of human TRPM4 in lipid nanodisc. This reconstruction includes only the cytoplasmic domain refined as a monomer, showing connectivity but fewer high-resolution features.
Sharpened 3D density map of human TRPM4 in lipid nanodisc. The reconstruction includes only the transmembrane domain and part of the cytoplasmic domain, refined with C4 symmetry
Sharpened 3D density map of human TRPM4 in lipid nanodisc. This reconstruction includes only the cytoplasmic domain refined as a monomer, showing high-resolution features but less connectivity.