6BWI

3.7 angstrom cryoEM structure of full length human TRPM4

Summary for 6BWI

• Entry DOI: 10.2210/pdb6bwi/pdb
• EMDB information: 7299
• Descriptor: Transient receptor potential cation channel subfamily M member 4, SODIUM ION, CHOLESTEROL HEMISUCCINATE, ... (4 entities in total)
• Functional Keywords: cryoem, human full length trpm7, membrane protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 430775.86

Authors

Zhang, J.,Li, Z.,Duan, J.,Li, J.,Clapham, D.E. (deposition date: 2017-12-15, release date: 2018-12-19, Last modification date: 2025-06-04)

Primary citation

Duan, J.,Li, Z.,Li, J.,Santa-Cruz, A.,Sanchez-Martinez, S.,Zhang, J.,Clapham, D.E.
Structure of full-length human TRPM4.
Proc.Natl.Acad.Sci.USA, 115:2377-2382, 2018

PubMed Abstract: Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel. Mutations in human TRPM4 (hTRPM4) result in progressive familial heart block. Here, we report the electron cryomicroscopy structure of hTRPM4 in a closed, Na-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å. Five partially hydrated sodium ions are proposed to occupy the center of the conduction pore and the entrance to the coiled-coil domain. We identify an upper gate in the selectivity filter and a lower gate at the entrance to the cytoplasmic coiled-coil domain. Intramolecular interactions exist between the TRP domain and the S4-S5 linker, N-terminal domain, and N and C termini. Finally, we identify aromatic interactions via π-π bonds and cation-π bonds, glycosylation at an N-linked extracellular site, a pore-loop disulfide bond, and 24 lipid binding sites. We compare and contrast this structure with other TRP channels and discuss potential mechanisms of regulation and gating of human full-length TRPM4.

PubMed: 29463718
DOI: 10.1073/pnas.1722038115

Experimental method

ELECTRON MICROSCOPY (3.7 Å)