Laboratory of Molecular Biology, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD, 20892, USA.
Laboratory of Membrane Proteins and Structural Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Nat Commun. 2020 Jul 3;11(1):3290. doi: 10.1038/s41467-020-17144-1.
In mitochondria, β-barrel outer membrane proteins mediate protein import, metabolite transport, lipid transport, and biogenesis. The Sorting and Assembly Machinery (SAM) complex consists of three proteins that assemble as a 1:1:1 complex to fold β-barrel proteins and insert them into the mitochondrial outer membrane. We report cryoEM structures of the SAM complex from Myceliophthora thermophila, which show that Sam50 forms a 16-stranded transmembrane β-barrel with a single polypeptide-transport-associated (POTRA) domain extending into the intermembrane space. Sam35 and Sam37 are located on the cytosolic side of the outer membrane, with Sam35 capping Sam50, and Sam37 interacting extensively with Sam35. Sam35 and Sam37 each adopt a GST-like fold, with no functional, structural, or sequence similarity to their bacterial counterparts. Structural analysis shows how the Sam50 β-barrel opens a lateral gate to accommodate its substrates.
在线粒体中，β-桶状外膜蛋白介导蛋白质导入、代谢物运输、脂质运输和生物发生。分选和装配机器（SAM）复合物由三种蛋白质组成，它们以 1:1:1 的比例组装，折叠β-桶状蛋白并将其插入线粒体外膜。我们报告了嗜热毁丝霉 SAM 复合物的冷冻电镜结构，该结构显示 Sam50 形成一个具有单个多肽转运相关（POTRA）结构域的 16 股跨膜β-桶，该结构域延伸到膜间空间。Sam35 和 Sam37 位于外膜的胞质侧，Sam35 覆盖 Sam50，Sam37 与 Sam35 广泛相互作用。Sam35 和 Sam37 各自采用 GST 样折叠，与细菌对应物在功能、结构或序列上没有相似性。结构分析显示了 Sam50 β-桶如何打开侧门以容纳其底物。
