- EMDB-23683: human ATP13A2 in the AMPPNP-bound occluded state -
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基本情報
登録情報
データベース: EMDB / ID: EMD-23683
タイトル
human ATP13A2 in the AMPPNP-bound occluded state
マップデータ
試料
複合体: Transport protein in an occluded state
タンパク質・ペプチド: x 1種
リガンド: x 10種
機能・相同性
機能・相同性情報
ABC-type polyamine transporter activity / polyamine transmembrane transport / spermine transmembrane transport / peptidyl-aspartic acid autophosphorylation / regulation of ubiquitin-specific protease activity / polyamine transmembrane transporter activity / regulation of autophagosome size / P-type ion transporter activity / extracellular exosome biogenesis / regulation of chaperone-mediated autophagy ...ABC-type polyamine transporter activity / polyamine transmembrane transport / spermine transmembrane transport / peptidyl-aspartic acid autophosphorylation / regulation of ubiquitin-specific protease activity / polyamine transmembrane transporter activity / regulation of autophagosome size / P-type ion transporter activity / extracellular exosome biogenesis / regulation of chaperone-mediated autophagy / negative regulation of lysosomal protein catabolic process / autophagosome-lysosome fusion / regulation of autophagy of mitochondrion / regulation of lysosomal protein catabolic process / intracellular monoatomic cation homeostasis / autophagosome organization / protein localization to lysosome / phosphatidic acid binding / multivesicular body membrane / positive regulation of exosomal secretion / ATPase-coupled monoatomic cation transmembrane transporter activity / intracellular zinc ion homeostasis / regulation of protein localization to nucleus / 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 / cupric ion binding / regulation of endopeptidase activity / regulation of mitochondrion organization / phosphatidylinositol-3,5-bisphosphate binding / cellular response to zinc ion / lysosomal transport / regulation of intracellular protein transport / lipid homeostasis / autophagosome membrane / Ion transport by P-type ATPases / autophagosome / cellular response to manganese ion / regulation of macroautophagy / regulation of neuron apoptotic process / monoatomic ion transmembrane transport / transport vesicle / multivesicular body / lysosomal lumen / positive regulation of protein secretion / transmembrane transport / autophagy / intracellular calcium ion homeostasis / late endosome / late endosome membrane / manganese ion binding / cellular response to oxidative stress / intracellular iron ion homeostasis / vesicle / protein autophosphorylation / 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
ジャーナル: Mol Cell / 年: 2021 タイトル: Structural mechanisms for gating and ion selectivity of the human polyamine transporter ATP13A2. 著者: Jordan Tillinghast / Sydney Drury / Darren Bowser / Alana Benn / Kenneth Pak Kin Lee / 要旨: Mutations in ATP13A2, also known as PARK9, cause a rare monogenic form of juvenile-onset Parkinson's disease named Kufor-Rakeb syndrome and other neurodegenerative diseases. ATP13A2 encodes a ...Mutations in ATP13A2, also known as PARK9, cause a rare monogenic form of juvenile-onset Parkinson's disease named Kufor-Rakeb syndrome and other neurodegenerative diseases. ATP13A2 encodes a neuroprotective P5B P-type ATPase highly enriched in the brain that mediates selective import of spermine ions from lysosomes into the cytosol via an unknown mechanism. Here we present three structures of human ATP13A2 bound to an ATP analog or to spermine in the presence of phosphomimetics determined by cryoelectron microscopy. ATP13A2 autophosphorylation opens a lysosome luminal gate to reveal a narrow lumen access channel that holds a spermine ion in its entrance. ATP13A2's architecture suggests physical principles underlying selective polyamine transport and anticipates a "pump-channel" intermediate that could function as a counter-cation conduit to facilitate lysosome acidification. Our findings establish a firm foundation to understand ATP13A2 mutations associated with disease and bring us closer to realizing ATP13A2's potential in neuroprotective therapy.