National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM079179
米国
Howard Hughes Medical Institute (HHMI)
米国
Welch Foundation
I-1578
米国
Virginia Murchison Linthicum Scholar in Medical Research fund
米国
Cancer Prevention and Research Institute of Texas (CPRIT)
米国
引用
ジャーナル: Nature / 年: 2017 タイトル: Structures of the calcium-activated, non-selective cation channel TRPM4. 著者: Jiangtao Guo / Ji She / Weizhong Zeng / Qingfeng Chen / Xiao-Chen Bai / Youxing Jiang / 要旨: 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 ...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.
タイプ: PROJECTION MATCHING / ソフトウェア - 名称: RELION (ver. 2) 詳細: Auto-refinement in Relion generated the final reconstruction. The angular sampling was determined automatically in Relion.
最終 3次元分類
クラス数: 8 / ソフトウェア - 名称: RELION (ver. 2) 詳細: A focused 3D classification at the coiled coil domain was performed.