EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structural basis for the activation of the lipid scramblase TMEM16F.
ジャーナル・号・ページ	Nat Commun, Vol. 13, Issue 1, Page 6692, Year 2022
掲載日	2022年11月5日
著者	Melanie Arndt / Carolina Alvadia / Monique S Straub / Vanessa Clerico Mosina / Cristina Paulino / Raimund Dutzler /
PubMed 要旨	TMEM16F, a member of the conserved TMEM16 family, plays a central role in the initiation of blood coagulation and the fusion of trophoblasts. The protein mediates passive ion and lipid transport in ...TMEM16F, a member of the conserved TMEM16 family, plays a central role in the initiation of blood coagulation and the fusion of trophoblasts. The protein mediates passive ion and lipid transport in response to an increase in intracellular Ca. However, the mechanism of how the protein facilitates both processes has remained elusive. Here we investigate the basis for TMEM16F activation. In a screen of residues lining the proposed site of conduction, we identify mutants with strongly activating phenotype. Structures of these mutants determined herein by cryo-electron microscopy show major rearrangements leading to the exposure of hydrophilic patches to the membrane, whose distortion facilitates lipid diffusion. The concomitant opening of a pore promotes ion conduction in the same protein conformation. Our work has revealed a mechanism that is distinct for this branch of the family and that will aid the development of a specific pharmacology for a promising drug target.
リンク	Nat Commun / PubMed:36335104 / PubMed Central
手法	EM (単粒子)
解像度	2.93 - 3.49 Å
構造データ	15913 8b8g EMDB-15913, PDB-8b8g: Cryo-EM structure of Ca2+-free mTMEM16F F518H mutant in Digitonin 手法: EM (単粒子) / 解像度: 3.39 Å 15914 8b8j EMDB-15914, PDB-8b8j: Cryo-EM structure of Ca2+-bound mTMEM16F F518H mutant in Digitonin 手法: EM (単粒子) / 解像度: 2.96 Å 15916 8b8k EMDB-15916, PDB-8b8k: Cryo-EM structure of Ca2+-bound mTMEM16F N562A mutant in Digitonin closed/closed 手法: EM (単粒子) / 解像度: 3.01 Å 15917 8b8m EMDB-15917, PDB-8b8m: Cryo-EM structure of Ca2+-bound mTMEM16F N562A mutant in Digitonin open/closed 手法: EM (単粒子) / 解像度: 3.49 Å 15919 8b8q EMDB-15919, PDB-8b8q: Structure of mTMEM16F in lipid Nanodiscs in the presence of Ca2+ 手法: EM (単粒子) / 解像度: 2.94 Å 15958 8bc0 EMDB-15958, PDB-8bc0: Cryo-EM structure of Ca2+-bound mTMEM16F F518A Q623A mutant in GDN open/closed 手法: EM (単粒子) / 解像度: 3.09 Å 15959 8bc1 EMDB-15959, PDB-8bc1: Cryo-EM Structure of Ca2+-bound mTMEM16F F518A_Q623A mutant in GDN 手法: EM (単粒子) / 解像度: 2.93 Å
化合物	ChemComp-CA: Unknown entry / カルシウムジカチオン ChemComp-P1O: 1,2-DIDECANOYL-SN-GLYCERO-3-PHOSPHOCHOLINE / ジデカノイルホスファチジルコリン / DDPC, リン脂質*YM
由来	mus musculus (ハツカネズミ)
キーワード	MEMBRANE PROTEIN / Lipid Transport / Lipid Scrambling / Ion Channel / Plasma Membrane / Blood Clotting / Exocytosis / Membrane Fusion / Lipid Scramblase / Blood Coagulation / Viral Entry / Cell Fusion