TOM complex / mitochondrion targeting sequence binding / mitochondrial outer membrane translocase complex / mitochondria-associated endoplasmic reticulum membrane contact site / protein import into mitochondrial matrix / positive regulation of type 2 mitophagy / Mitochondrial protein import / protein targeting to mitochondrion / positive regulation of protein targeting to mitochondrion / porin activity ...TOM complex / mitochondrion targeting sequence binding / mitochondrial outer membrane translocase complex / mitochondria-associated endoplasmic reticulum membrane contact site / protein import into mitochondrial matrix / positive regulation of type 2 mitophagy / Mitochondrial protein import / protein targeting to mitochondrion / positive regulation of protein targeting to mitochondrion / porin activity / pore complex / protein insertion into mitochondrial outer membrane / protein transmembrane transporter activity / monoatomic ion transport / PINK1-PRKN Mediated Mitophagy / regulation of protein stability / mitochondrial outer membrane / mitochondrial inner membrane / mitochondrion / membrane / cytosol 類似検索 - 分子機能
National Basic Research Program of China (973 Program)
中国
引用
ジャーナル: Proc Natl Acad Sci U S A / 年: 2022 タイトル: Structural basis of Tom20 and Tom22 cytosolic domains as the human TOM complex receptors. 著者: Jiayue Su / Desheng Liu / Fan Yang / Mei-Qing Zuo / Chang Li / Meng-Qiu Dong / Shan Sun / Sen-Fang Sui / 要旨: Mitochondrial preproteins synthesized in cytosol are imported into mitochondria by a multisubunit translocase of the outer membrane (TOM) complex. Functioned as the receptor, the TOM complex ...Mitochondrial preproteins synthesized in cytosol are imported into mitochondria by a multisubunit translocase of the outer membrane (TOM) complex. Functioned as the receptor, the TOM complex components, Tom 20, Tom22, and Tom70, recognize the presequence and further guide the protein translocation. Their deficiency has been linked with neurodegenerative diseases and cardiac pathology. Although several structures of the TOM complex have been reported by cryoelectron microscopy (cryo-EM), how Tom22 and Tom20 function as TOM receptors remains elusive. Here we determined the structure of TOM core complex at 2.53 Å and captured the structure of the TOM complex containing Tom22 and Tom20 cytosolic domains at 3.74 Å. Structural analysis indicates that Tom20 and Tom22 share a similar three-helix bundle structural feature in the cytosolic domain. Further structure-guided biochemical analysis reveals that the Tom22 cytosolic domain is responsible for binding to the presequence, and the helix H1 is critical for this binding. Altogether, our results provide insights into the functional mechanism of the TOM complex recognizing and transferring preproteins across the mitochondrial membrane.