AAA protein / mitochondria (ミトコンドリア) / tail-anchored protein / membrane protein (膜タンパク質) / PROTEIN TRANSPORT
機能・相同性
機能・相同性情報
extraction of mislocalized protein from mitochondrial outer membrane / membrane protein dislocase activity / Class I peroxisomal membrane protein import / Translocases; Catalysing the translocation of amino acids and peptides; Linked to the hydrolysis of a nucleoside triphosphate / negative regulation of synaptic transmission, glutamatergic / regulation of postsynaptic neurotransmitter receptor internalization / peroxisomal membrane / positive regulation of receptor internalization / 学習 / 記憶 ...extraction of mislocalized protein from mitochondrial outer membrane / membrane protein dislocase activity / Class I peroxisomal membrane protein import / Translocases; Catalysing the translocation of amino acids and peptides; Linked to the hydrolysis of a nucleoside triphosphate / negative regulation of synaptic transmission, glutamatergic / regulation of postsynaptic neurotransmitter receptor internalization / peroxisomal membrane / positive regulation of receptor internalization / 学習 / 記憶 / postsynaptic membrane / mitochondrial outer membrane / glutamatergic synapse / ATP hydrolysis activity / ATP binding / 生体膜 / 細胞質基質 類似検索 - 分子機能
AAA ATPase, AAA+ lid domain / AAA+ lid domain / ATPase, AAA-type, conserved site / AAA-protein family signature. / ATPase family associated with various cellular activities (AAA) / ATPase, AAA-type, core / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM032384
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
S10OD021741
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
S10OD020054
米国
引用
ジャーナル: Elife / 年: 2022 タイトル: Conserved structural elements specialize ATAD1 as a membrane protein extraction machine. 著者: Lan Wang / Hannah Toutkoushian / Vladislav Belyy / Claire Y Kokontis / Peter Walter / 要旨: The mitochondrial AAA (TPase ssociated with diverse cellular ctivities) protein ATAD1 (in humans; Msp1 in yeast) removes mislocalized membrane proteins, as well as stuck import substrates from the ...The mitochondrial AAA (TPase ssociated with diverse cellular ctivities) protein ATAD1 (in humans; Msp1 in yeast) removes mislocalized membrane proteins, as well as stuck import substrates from the mitochondrial outer membrane, facilitating their re-insertion into their cognate organelles and maintaining mitochondria's protein import capacity. In doing so, it helps to maintain proteostasis in mitochondria. How ATAD1 tackles the energetic challenge to extract hydrophobic membrane proteins from the lipid bilayer and what structural features adapt ATAD1 for its particular function has remained a mystery. Previously, we determined the structure of Msp1 in complex with a peptide substrate (Wang et al., 2020). The structure showed that Msp1's mechanism follows the general principle established for AAA proteins while adopting several structural features that specialize it for its function. Among these features in Msp1 was the utilization of multiple aromatic amino acids to firmly grip the substrate in the central pore. However, it was not clear whether the aromatic nature of these amino acids were required, or if they could be functionally replaced by aliphatic amino acids. In this work, we determined the cryo-EM structures of the human ATAD1 in complex with a peptide substrate at near atomic resolution. The structures show that phylogenetically conserved structural elements adapt ATAD1 for its function while generally adopting a conserved mechanism shared by many AAA proteins. We developed a microscopy-based assay reporting on protein mislocalization, with which we directly assessed ATAD1's activity in live cells and showed that both aromatic amino acids in pore-loop 1 are required for ATAD1's function and cannot be substituted by aliphatic amino acids. A short α-helix at the C-terminus strongly facilitates ATAD1's oligomerization, a structural feature that distinguishes ATAD1 from its closely related proteins.