{"title":"Structural overview of the translocase of the mitochondrial outer membrane complex.","authors":"Yuhei Araiso, Toshiya Endo","doi":"10.2142/biophysico.bppb-v19.0022","DOIUrl":null,"url":null,"abstract":"<p><p>Most mitochondrial proteins are synthesized as precursor proteins (preproteins) in the cytosol and imported into mitochondria. The translocator of the outer membrane (TOM) complex functions as a main entry gate for the import of mitochondrial proteins. The TOM complex is a multi-subunit membrane protein complex composed of a β-barrel channel Tom40 and six single-pass membrane proteins. Recent cryo-EM studies have revealed high-resolution structures of the yeast and human TOM complexes, which enabled us to discuss the mechanism of protein import at an amino-acid residue level. The cryo-EM structures show that two Tom40 β-barrels are surrounded by two sets of small Tom subunits to form a dimeric structure. The intermembrane space (IMS) domains of Tom40, Tom22, and Tom7 form a binding site for presequence-containing preproteins in the middle of the dimer to achieve their efficient transfer of to the downstream translocase, the TIM23 complex. The N-terminal segment of Tom40 spans the channel from the cytosol to the IMS to interact with Tom5 at the periphery of the dimer, where downstream components of presequence-lacking preproteins are recruited. Structure-based biochemical analyses together with crosslinking experiments revealed that each Tom40 channel possesses two distinct paths and exit sites for protein translocation of different sets of mitochondrial preproteins. Here we summarize the current knowledge on the structural features, protein translocation mechanisms, and remaining questions for the TOM complexes, with particular emphasis on their determined cryo-EM structures. This article is an extended version of the Japanese article, Structural basis for protein translocation by the translocase of the outer mitochondrial membrane, published in SEIBUTSU BUTSURI Vol. 60, p. 280-283 (2020).</p>","PeriodicalId":8976,"journal":{"name":"Biophysics and Physicobiology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2022-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/be/b1/19_e190022.PMC9260164.pdf","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biophysics and Physicobiology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2142/biophysico.bppb-v19.0022","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/1/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 1
Abstract
Most mitochondrial proteins are synthesized as precursor proteins (preproteins) in the cytosol and imported into mitochondria. The translocator of the outer membrane (TOM) complex functions as a main entry gate for the import of mitochondrial proteins. The TOM complex is a multi-subunit membrane protein complex composed of a β-barrel channel Tom40 and six single-pass membrane proteins. Recent cryo-EM studies have revealed high-resolution structures of the yeast and human TOM complexes, which enabled us to discuss the mechanism of protein import at an amino-acid residue level. The cryo-EM structures show that two Tom40 β-barrels are surrounded by two sets of small Tom subunits to form a dimeric structure. The intermembrane space (IMS) domains of Tom40, Tom22, and Tom7 form a binding site for presequence-containing preproteins in the middle of the dimer to achieve their efficient transfer of to the downstream translocase, the TIM23 complex. The N-terminal segment of Tom40 spans the channel from the cytosol to the IMS to interact with Tom5 at the periphery of the dimer, where downstream components of presequence-lacking preproteins are recruited. Structure-based biochemical analyses together with crosslinking experiments revealed that each Tom40 channel possesses two distinct paths and exit sites for protein translocation of different sets of mitochondrial preproteins. Here we summarize the current knowledge on the structural features, protein translocation mechanisms, and remaining questions for the TOM complexes, with particular emphasis on their determined cryo-EM structures. This article is an extended version of the Japanese article, Structural basis for protein translocation by the translocase of the outer mitochondrial membrane, published in SEIBUTSU BUTSURI Vol. 60, p. 280-283 (2020).
大多数线粒体蛋白在细胞质中作为前体蛋白(preprotein)合成并导入线粒体。外膜转运子(TOM)复合物是线粒体蛋白输入的主要入口。TOM复合物是一种多亚基膜蛋白复合物,由一个β桶通道Tom40和6个单通膜蛋白组成。最近的冷冻电镜研究揭示了酵母和人类TOM复合物的高分辨率结构,这使我们能够在氨基酸残留水平上讨论蛋白质进口的机制。低温电镜结构表明,两个Tom40 β-桶被两组小的Tom亚基包围,形成二聚体结构。Tom40、Tom22和Tom7的膜间空间(IMS)结构域在二聚体中间形成含有序列的前蛋白的结合位点,以实现它们向下游转位酶TIM23复合物的有效转移。Tom40的n端片段跨越从细胞质到IMS的通道,在二聚体的外围与Tom5相互作用,在那里招募了缺乏序列的前蛋白的下游组分。基于结构的生化分析和交联实验表明,每个Tom40通道具有不同线粒体前蛋白组蛋白质易位的两个不同路径和出口位点。在这里,我们总结了目前对TOM复合物的结构特征、蛋白质易位机制和遗留问题的了解,特别强调了它们确定的低温电镜结构。本文是日本文章《the translocase for protein translocation by the outer mitochondrial membrane的结构基础》的扩展版,发表于SEIBUTSU BUTSURI Vol. 60, p. 280-283(2020)。