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 mechanism of allosteric activation of TRPML1 by PI(3,5)P and rapamycin.
ジャーナル・号・ページ	Proc Natl Acad Sci U S A, Vol. 119, Issue 7, Year 2022
掲載日	2022年2月15日
著者	Ninghai Gan / Yan Han / Weizhong Zeng / Yan Wang / Jing Xue / Youxing Jiang /
PubMed 要旨	Transient receptor potential mucolipin 1 (TRPML1) is a Ca-permeable, nonselective cation channel ubiquitously expressed in the endolysosomes of mammalian cells and its loss-of-function mutations are ...Transient receptor potential mucolipin 1 (TRPML1) is a Ca-permeable, nonselective cation channel ubiquitously expressed in the endolysosomes of mammalian cells and its loss-of-function mutations are the direct cause of type IV mucolipidosis (MLIV), an autosomal recessive lysosomal storage disease. TRPML1 is a ligand-gated channel that can be activated by phosphatidylinositol 3,5-bisphosphate [PI(3,5)P] as well as some synthetic small-molecule agonists. Recently, rapamycin has also been shown to directly bind and activate TRPML1. Interestingly, both PI(3,5)P and rapamycin have low efficacy in channel activation individually but together they work cooperatively and activate the channel with high potency. To reveal the structural basis underlying the synergistic activation of TRPML1 by PI(3,5)P and rapamycin, we determined the high-resolution cryoelectron microscopy (cryo-EM) structures of the mouse TRPML1 channel in various states, including apo closed, PI(3,5)P-bound closed, and PI(3,5)P/temsirolimus (a rapamycin analog)-bound open states. These structures, combined with electrophysiology, elucidate the molecular details of ligand binding and provide structural insight into how the TRPML1 channel integrates two distantly bound ligand stimuli and facilitates channel opening.
リンク	Proc Natl Acad Sci U S A / PubMed:35131932 / PubMed Central
手法	EM (単粒子)
解像度	2.11 - 2.598 Å
構造データ	25377 7sq6 EMDB-25377, PDB-7sq6: Cryo-EM structure of mouse agonist ML-SA1-bound TRPML1 channel at 2.32 Angstrom resolution 手法: EM (単粒子) / 解像度: 2.32 Å 25378 7sq7 EMDB-25378, PDB-7sq7: Cryo-EM structure of mouse PI(3,5)P2-bound TRPML1 channel at 2.41 Angstrom resolution 手法: EM (単粒子) / 解像度: 2.41 Å 25379 7sq8 EMDB-25379, PDB-7sq8: Cryo-EM structure of mouse apo TRPML1 channel at 2.598 Angstrom resolution 手法: EM (単粒子) / 解像度: 2.598 Å 25380 7sq9 EMDB-25380, PDB-7sq9: Cryo-EM structure of mouse temsirolimus/PI(3,5)P2-bound TRPML1 channel at 2.11 Angstrom resolution 手法: EM (単粒子) / 解像度: 2.11 Å
化合物	ChemComp-AQV: 2-{2-oxo-2-[(4S)-2,2,4-trimethyl-3,4-dihydroquinolin-1(2H)-yl]ethyl}-1H-isoindole-1,3(2H)-dione ChemComp-NA: Unknown entry / ナトリウムカチオン ChemComp-HOH: WATER ChemComp-EUJ: (2R)-3-{[(S)-hydroxy{[(1S,2R,3R,4S,5S,6R)-2,4,6-trihydroxy-3,5-bis(phosphonooxy)cyclohexyl]oxy}phosphoryl]oxy}propane-1,2-diyl dioctanoate / L-myo-イノシト-ル1,3,5-トリスりん酸3-[(2R)-2,3-ビス(オクタノイルオキシ)プロピル] ChemComp-A4I: (1R,2R,4S)-4-{(2R)-2-[(3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,30S,34aS)-9,27-dihydroxy-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-1,5,11,28,29-pentaoxo-1,4,5,6,9,10,11,12,13,14,21,22,23,24,25,26,27,28,29,31,32,33,34,34a-tetracosahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontin-3-yl]propyl}-2-methoxycyclohexyl 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate
由来	mus musculus (ハツカネズミ)
キーワード	MEMBRANE PROTEIN / ion channel