Title : Structure of the human TRPM4 ion channel in a lipid nanodisc
Abstract :
Transient receptor potential ( TRP ) melastatin 4 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