- EMDB-31627: Cryo EM structure of lysosomal ATPase -
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基本情報
登録情報
データベース: EMDB / ID: EMD-31627
タイトル
Cryo EM structure of lysosomal ATPase
マップデータ
試料
細胞器官・細胞要素: Lysosomal ATPase E2Pi state
タンパク質・ペプチド: Polyamine-transporting ATPase 13A2
リガンド: SPERMINE
キーワード
lysosomal ATPase transporter / MEMBRANE PROTEIN
機能・相同性
機能・相同性情報
polyamine transmembrane transporter activity / polyamine transmembrane transport / spermine transmembrane transport / : / ABC-type polyamine transporter activity / regulation of autophagosome size / extracellular exosome biogenesis / regulation of chaperone-mediated autophagy / negative regulation of lysosomal protein catabolic process / regulation of autophagy of mitochondrion ...polyamine transmembrane transporter activity / polyamine transmembrane transport / spermine transmembrane transport / : / ABC-type polyamine transporter activity / regulation of autophagosome size / extracellular exosome biogenesis / regulation of chaperone-mediated autophagy / negative regulation of lysosomal protein catabolic process / regulation of autophagy of mitochondrion / P-type ion transporter activity / regulation of lysosomal protein catabolic process / intracellular monoatomic cation homeostasis / autophagosome-lysosome fusion / protein localization to lysosome / autophagosome organization / phosphatidic acid binding / positive regulation of exosomal secretion / multivesicular body membrane / ATPase-coupled monoatomic cation transmembrane transporter activity / regulation of protein localization to nucleus / intracellular zinc ion homeostasis / cupric ion binding / phosphatidylinositol-3,5-bisphosphate binding / regulation of mitochondrion organization / トランスロカーゼ; 他の化合物の輸送を触媒; ヌクレオシド三リン酸の加水分解に伴う / cellular response to zinc ion / lysosomal transport / regulation of intracellular protein transport / lipid homeostasis / Ion transport by P-type ATPases / autophagosome membrane / cellular response to manganese ion / regulation of macroautophagy / transport vesicle / regulation of neuron apoptotic process / multivesicular body / lysosomal lumen / autophagosome / positive regulation of protein secretion / autophagy / intracellular calcium ion homeostasis / late endosome membrane / late endosome / manganese ion binding / cellular response to oxidative stress / monoatomic ion transmembrane transport / vesicle / intracellular iron ion homeostasis / lysosome / neuron projection / lysosomal membrane / neuronal cell body / positive regulation of gene expression / ATP hydrolysis activity / zinc ion binding / ATP binding / membrane 類似検索 - 分子機能
National Natural Science Foundation of China (NSFC)
21532004, 31570733
中国
引用
ジャーナル: Cell Discov / 年: 2021 タイトル: Cryo-EM structures and transport mechanism of human P5B type ATPase ATP13A2. 著者: Xudong Chen / Mingze Zhou / Sensen Zhang / Jian Yin / Ping Zhang / Xujun Xuan / Peiyi Wang / Zhiqiang Liu / Boda Zhou / Maojun Yang / 要旨: Polyamines are important polycations that play critical roles in mammalian cells. ATP13A2 belongs to the orphan P5B adenosine triphosphatases (ATPase) family and has been established as a lysosomal ...Polyamines are important polycations that play critical roles in mammalian cells. ATP13A2 belongs to the orphan P5B adenosine triphosphatases (ATPase) family and has been established as a lysosomal polyamine exporter to maintain the normal function of lysosomes and mitochondria. Previous studies have reported that several human neurodegenerative disorders are related to mutations in the ATP13A2 gene. However, the transport mechanism of ATP13A2 in the lysosome remains unclear. Here, we report the cryo-electron microscopy (cryo-EM) structures of three distinct intermediates of the human ATP13A2, revealing key insights into the spermine (SPM) transport cycle in the lysosome. The transmembrane domain serves as a substrate binding site and the C-terminal domain is essential for protein stability and may play a regulatory role. These findings advance our understanding of the polyamine transport mechanism, the lipid-associated regulation, and the disease-associated mutants of ATP13A2.