6BQV

Human TRPM4 ion channel in lipid nanodiscs in a calcium-bound state

Summary for 6BQV

• Entry DOI: 10.2210/pdb6bqv/pdb
• EMDB information: 7132 7133
• Descriptor: Transient receptor potential cation channel subfamily M member 4, CALCIUM ION, CHOLESTEROL HEMISUCCINATE (3 entities in total)
• Functional Keywords: trpm4, trpm channel, trp channel, membrane protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 545083.96

Authors

Autzen, H.E.,Myasnikov, A.G.,Campbell, M.G.,Asarnow, D.,Julius, D.,Cheng, Y. (deposition date: 2017-11-28, release date: 2017-12-20, Last modification date: 2024-03-13)

Primary citation

Autzen, H.E.,Myasnikov, A.G.,Campbell, M.G.,Asarnow, D.,Julius, D.,Cheng, Y.
Structure of the human TRPM4 ion channel in a lipid nanodisc.
Science, 359:228-232, 2018

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.

PubMed: 29217581
DOI: 10.1126/science.aar4510

Experimental method

ELECTRON MICROSCOPY (3.1 Å)