@article {49057,
	title = {Structure of full-length human TRPM4.},
	journal = {Proceedings of the National Academy of Sciences of the United States of America},
	volume = {115},
	year = {2018},
	month = {2018 Feb 20},
	pages = {2377-82},
	abstract = {<p>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 {\r A}. 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.</p>
},
	issn = {1091-6490},
	doi = {10.1073/pnas.1722038115},
	author = {Duan, Jingjing and Li, Zongli and Li, Jian and Santa-Cruz, Ana and Sanchez-Martinez, Silvia and Zhang, Jin and Clapham, David E}
}
