小柯机器人

日本京都产业大学生命科学学院Toshiya Endo研究组取得最新进展。他们提出线粒体线粒体分选和组装机器（SAM，也称为TOB）由β-桶转换操纵。该研究于2021年1月6日发表于《自然》杂志。

他们使用冷冻电子显微镜确定分辨率为2.8–3.2Å的两种不同形式的酵母SAM复合物的结构。该二聚体复合物包含两个拷贝的β-桶形通道蛋白Sam50-Sam50a和Sam50b-具有部分开放侧门。外周膜蛋白Sam35和Sam37从胞质侧覆盖Sam50通道，对于二聚体复合物的结构和功能完整性至关重要。在第二种复合物中，Sam50b被β-桶蛋白Mdm10取代。与Sam50a协同作用，Sam37通过从胞质侧穿透其侧面封闭的β-桶内部来招募和捕获Mdm10。装载有底物的SAM复合物分别包含Sam50、Sam35和Sam37中的一种，但既没有Mdm10，也没有第二种Sam50，这表明Mdm10和Sam50b充当从Sam50a释放β-桶底物的占位符。

他们提出的用于动态切换β-桶亚基和底物的机制解释了整个前体蛋白如何与β-桶装配的线粒体机制折叠在一起

据了解，线粒体的外膜含有所谓的β-桶状蛋白，可以使细胞质与线粒体内部之间发生通讯。 β-桶蛋白插入外膜是由多亚基线粒体SAM介导的。

附：英文原文

Title: Mitochondrial sorting and assembly machinery operates by β-barrel switching

Author: Hironori Takeda, Akihisa Tsutsumi, Tomohiro Nishizawa, Caroline Lindau, Jon V. Busto, Lena-Sophie Wenz, Lars Ellenrieder, Kenichiro Imai, Sebastian P. Straub, Waltraut Mossmann, Jian Qiu, Yu Yamamori, Kentaro Tomii, Junko Suzuki, Takeshi Murata, Satoshi Ogasawara, Osamu Nureki, Thomas Becker, Nikolaus Pfanner, Nils Wiedemann, Masahide Kikkawa, Toshiya Endo

Issue&Volume: 2021-01-06

Abstract: The mitochondrial outer membrane contains so-called β-barrel proteins, which allow communication between the cytosol and the mitochondrial interior1,2,3. Insertion of β-barrel proteins into the outer membrane is mediated by the multisubunit mitochondrial sorting and assembly machinery (SAM, also known as TOB)4,5,6. Here we use cryo-electron microscopy to determine the structures of two different forms of the yeast SAM complex at a resolution of 2.8–3.2 . The dimeric complex contains two copies of the β-barrel channel protein Sam50—Sam50a and Sam50b—with partially open lateral gates. The peripheral membrane proteins Sam35 and Sam37 cap the Sam50 channels from the cytosolic side, and are crucial for the structural and functional integrity of the dimeric complex. In the second complex, Sam50b is replaced by the β-barrel protein Mdm10. In cooperation with Sam50a, Sam37 recruits and traps Mdm10 by penetrating the interior of its laterally closed β-barrel from the cytosolic side. The substrate-loaded SAM complex contains one each of Sam50, Sam35 and Sam37, but neither Mdm10 nor a second Sam50, suggesting that Mdm10 and Sam50b function as placeholders for a β-barrel substrate released from Sam50a. Our proposed mechanism for dynamic switching of β-barrel subunits and substrate explains how entire precursor proteins can fold in association with the mitochondrial machinery for β-barrel assembly.

DOI: 10.1038/s41586-020-03113-7

Source: https://www.nature.com/articles/s41586-020-03113-7

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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