5WP6

Cryo-EM structure of a human TRPM4 channel in complex with calcium and decavanadate

Summary for 5WP6

• Entry DOI: 10.2210/pdb5wp6/pdb
• EMDB information: 8871 8872 8875 8876 8877 8878 8879
• Descriptor: Transient receptor potential cation channel subfamily M member 4, DECAVANADATE (2 entities in total)
• Functional Keywords: ion channel, membrane protein
• Biological source: Homo sapiens (Human)
• Cellular location: Isoform 1: Cell membrane; Multi-pass membrane protein. Isoform 2: Endoplasmic reticulum: Q8TD43
• Total number of polymer chains: 4
• Total formula weight: 545485.12

Authors

Winkler, P.A.,Huang, Y.,Sun, W.,Du, J.,Lu, W. (deposition date: 2017-08-03, release date: 2017-12-13, Last modification date: 2024-05-15)

Primary citation

Winkler, P.A.,Huang, Y.,Sun, W.,Du, J.,Lu, W.
Electron cryo-microscopy structure of a human TRPM4 channel.
Nature, 552:200-204, 2017

PubMed Abstract: Ca-activated, non-selective (CAN) ion channels sense increases of the intracellular Ca concentration, producing a flux of Na and/or K ions that depolarizes the cell, thus modulating cellular Ca entry. CAN channels are involved in cellular responses such as neuronal bursting activity and cardiac rhythm. Here we report the electron cryo-microscopy structure of the most widespread CAN channel, human TRPM4, bound to the agonist Ca and the modulator decavanadate. Four cytosolic C-terminal domains form an umbrella-like structure with a coiled-coil domain for the 'pole' and four helical 'ribs' spanning the N-terminal TRPM homology regions (MHRs), thus holding four subunits in a crown-like architecture. We observed two decavanadate-binding sites, one in the C-terminal domain and another in the intersubunit MHR interface. A glutamine in the selectivity filter may be an important determinant of monovalent selectivity. Our structure provides new insights into the function and pharmacology of both the CAN and the TRPM families.

PubMed: 29211723
DOI: 10.1038/nature24674

Experimental method

ELECTRON MICROSCOPY (3.8 Å)