| First Author | Guo J | Year | 2017 |
| Journal | Nature | Volume | 552 |
| Issue | 7684 | Pages | 205-209 |
| PubMed ID | 29211714 | Mgi Jnum | J:257315 |
| Mgi Id | MGI:6119829 | Doi | 10.1038/nature24997 |
| Citation | Guo J, et al. (2017) Structures of the calcium-activated, non-selective cation channel TRPM4. Nature 552(7684):205-209 |
| abstractText | TRPM4 is a calcium-activated, phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) -modulated, non-selective cation channel that belongs to the family of melastatin-related transient receptor potential (TRPM) channels. Here we present the electron cryo-microscopy structures of the mouse TRPM4 channel with and without ATP. TRPM4 consists of multiple transmembrane and cytosolic domains, which assemble into a three-tiered architecture. The N-terminal nucleotide-binding domain and the C-terminal coiled-coil participate in the tetrameric assembly of the channel; ATP binds at the nucleotide-binding domain and inhibits channel activity. TRPM4 has an exceptionally wide filter but is only permeable to monovalent cations; filter residue Gln973 is essential in defining monovalent selectivity. The S1-S4 domain and the post-S6 TRP domain form the central gating apparatus that probably houses the Ca(2+)- and PtdIns(4,5)P2-binding sites. These structures provide an essential starting point for elucidating the complex gating mechanisms of TRPM4 and reveal the molecular architecture of the TRPM family. |
