- PDB-7n70: Cryo-EM structure of ATP13A2 in the BeF-bound E2P-like state -
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基本情報
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データベース: PDB / ID: 7n70
タイトル
Cryo-EM structure of ATP13A2 in the BeF-bound E2P-like state
要素
Isoform 3 of Polyamine-transporting ATPase 13A2
キーワード
TRANSPORT PROTEIN / P-type ATPase / P5B-ATPase / polyamine transporter
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
ジャーナル: Mol Cell / 年: 2021 タイトル: Structural basis of polyamine transport by human ATP13A2 (PARK9). 著者: Sue Im Sim / Sören von Bülow / Gerhard Hummer / Eunyong Park / 要旨: Polyamines are small, organic polycations that are ubiquitous and essential to all forms of life. Currently, how polyamines are transported across membranes is not understood. Recent studies have ...Polyamines are small, organic polycations that are ubiquitous and essential to all forms of life. Currently, how polyamines are transported across membranes is not understood. Recent studies have suggested that ATP13A2 and its close homologs, collectively known as P5B-ATPases, are polyamine transporters at endo-/lysosomes. Loss-of-function mutations of ATP13A2 in humans cause hereditary early-onset Parkinson's disease. To understand the polyamine transport mechanism of ATP13A2, we determined high-resolution cryoelectron microscopy (cryo-EM) structures of human ATP13A2 in five distinct conformational intermediates, which together, represent a near-complete transport cycle of ATP13A2. The structural basis of the polyamine specificity was revealed by an endogenous polyamine molecule bound to a narrow, elongated cavity within the transmembrane domain. The structures show an atypical transport path for a water-soluble substrate, in which polyamines may exit within the cytosolic leaflet of the membrane. Our study provides important mechanistic insights into polyamine transport and a framework to understand the functions and mechanisms of P5B-ATPases.
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2021年6月9日
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