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	Calcium dependent activation of the TMEM16F scramblase and ion channel.
ジャーナル・号・ページ	Nat Struct Mol Biol, Vol. 33, Issue 4, Page 664-676, Year 2026
掲載日	2026年4月17日
著者	Zhang Feng / Omar E Alvarenga / Eleonora Di Zanni / Sangyun Lee / George Khelashvili / Alessio Accardi /
PubMed 要旨	The ubiquitous transmembrane protein 16F (TMEM16F) Ca-activated channel and scramblase catalyzes phosphatidylserine externalization to enable blood coagulation, membrane fusion and brain immune ...The ubiquitous transmembrane protein 16F (TMEM16F) Ca-activated channel and scramblase catalyzes phosphatidylserine externalization to enable blood coagulation, membrane fusion and brain immune surveillance. Despite its importance, the molecular mechanisms underlying TMEM16F activation remain poorly understood. Here, we obtained high-resolution cryo-electron microscopy structures of TMEM16F active in liposomes. In high-activity conditions, TMEM16F adopts two conformations, the canonical Ca-bound closed state and one where the upward rotation of the cytosolic domain leads to an X-shaped groove that forms a transmembrane pore and locally thins the membrane. Using mutagenesis, functional assays and molecular dynamics simulations, we show that the X-shaped groove is active and mediates nonselective ion flux and lipid scrambling through distinct pathways; ions move within the protein-delimited pore, whereas lipids skirt the X-shaped groove. Our findings provide a complete picture of TMEM16F Ca-dependent gating and demonstrate that imaging membrane proteins in a native-like environment can allow capturing otherwise inaccessible active states.
リンク	Nat Struct Mol Biol / PubMed:41998358 / PubMed Central
手法	EM (単粒子)
解像度	2.49 - 4.2 Å
構造データ	70008 9o1i EMDB-70008, PDB-9o1i: TMEM16F in liposomes in the absence of Ca2+ (contracted state) 手法: EM (単粒子) / 解像度: 2.49 Å 70011 9o1l EMDB-70011, PDB-9o1l: TMEM16F in liposomes in the absence of Ca2+ (expanded state) 手法: EM (単粒子) / 解像度: 2.91 Å 70012 9o1m EMDB-70012, PDB-9o1m: TMEM16F in liposomes in the presence of Ca2+ (closed state) 手法: EM (単粒子) / 解像度: 2.92 Å 70013 9o1n EMDB-70013, PDB-9o1n: TMEM16F in liposomes in the presence of Ca2+ (active state) 手法: EM (単粒子) / 解像度: 3.56 Å 70014 9o1o EMDB-70014, PDB-9o1o: TMEM16F R478E/E604R mutant in liposomes in the presence of Ca2+ 手法: EM (単粒子) / 解像度: 2.97 Å 70015 9o1p EMDB-70015, PDB-9o1p: TMEM16F D409G mutant in liposomes in the presence of Ca2+ (closed state) 手法: EM (単粒子) / 解像度: 3.48 Å 70017 9o1q EMDB-70017, PDB-9o1q: TMEM16F D409G mutant in liposomes in the presence of Ca2+ (active state) 手法: EM (単粒子) / 解像度: 4.2 Å
化合物	ChemComp-PGW: (1R)-2-{[(S)-{[(2S)-2,3-dihydroxypropyl]oxy}(hydroxy)phosphoryl]oxy}-1-[(hexadecanoyloxy)methyl]ethyl / リン脂質YM ChemComp-CA*: Unknown entry
由来	mus musculus (ハツカネズミ)
キーワード	LIPID TRANSPORT / membrane protein / lipid scramblase / TMEM16 / liposome