Details

Autor(en) / Beteiligte

• Guo, Jiangtao
• She, Ji
• Zeng, Weizhong
• Chen, Qingfeng
• Bai, Xiao-Chen
• Jiang, Youxing

Titel

Structures of the calcium-activated, non-selective cation channel TRPM4

Ist Teil von

• Nature (London), 2017-12, Vol.552 (7684), p.205-209

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• TRPM4 is a calcium-activated, phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P ) -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 - and PtdIns(4,5)P -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.