+
検索条件

キーワード
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

-
Structure paper

タイトル	Cryo-EM structures of the human endolysosomal TRPML3 channel in three distinct states.
ジャーナル・号・ページ	Nat Struct Mol Biol, Vol. 24, Issue 12, Page 1146-1154, Year 2017
掲載日	2017年11月6日
著者	Xiaoyuan Zhou / Minghui Li / Deyuan Su / Qi Jia / Huan Li / Xueming Li / Jian Yang /
PubMed 要旨	TRPML3 channels are mainly localized to endolysosomes and play a critical role in the endocytic pathway. Their dysfunction causes deafness and pigmentation defects in mice. TRPML3 activity is ...TRPML3 channels are mainly localized to endolysosomes and play a critical role in the endocytic pathway. Their dysfunction causes deafness and pigmentation defects in mice. TRPML3 activity is inhibited by low endolysosomal pH. Here we present cryo-electron microscopy (cryo-EM) structures of human TRPML3 in the closed, agonist-activated, and low-pH-inhibited states, with resolutions of 4.06, 3.62, and 4.65 Å, respectively. The agonist ML-SA1 lodges between S5 and S6 and opens an S6 gate. A polycystin-mucolipin domain (PMD) forms a luminal cap. S1 extends into this cap, forming a 'gating rod' that connects directly to a luminal pore loop, which undergoes dramatic conformational changes in response to low pH. S2 extends intracellularly and interacts with several intracellular regions to form a 'gating knob'. These unique structural features, combined with the results of electrophysiological studies, indicate a new mechanism by which luminal pH and other physiological modulators such as PIP regulate TRPML3 by changing S1 and S2 conformations.
リンク	Nat Struct Mol Biol / PubMed:29106414 / PubMed Central
手法	EM (単粒子)
解像度	3.62 - 4.65 Å
構造データ	7018 6aye EMDB-7018, PDB-6aye: Human apo-TRPML3 channel at pH 7.4 手法: EM (単粒子) / 解像度: 4.06 Å 7019 6ayf EMDB-7019, PDB-6ayf: TRPML3/ML-SA1 complex at pH 7.4 手法: EM (単粒子) / 解像度: 3.62 Å 7020 6ayg EMDB-7020, PDB-6ayg: Human Apo-TRPML3 channel at pH 4.8 手法: EM (単粒子) / 解像度: 4.65 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン
由来	homo sapiens (ヒト)
キーワード	TRANSPORT PROTEIN / ion channel / TRP channel / lysosomal