Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, 17165 Solna, Stockholm, Sweden.
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden.
Science. 2021 Feb 19;371(6531):846-849. doi: 10.1126/science.abe0763.
Mitochondrial ribosomes (mitoribosomes) are tethered to the mitochondrial inner membrane to facilitate the cotranslational membrane insertion of the synthesized proteins. We report cryo-electron microscopy structures of human mitoribosomes with nascent polypeptide, bound to the insertase oxidase assembly 1-like (OXA1L) through three distinct contact sites. OXA1L binding is correlated with a series of conformational changes in the mitoribosomal large subunit that catalyze the delivery of newly synthesized polypeptides. The mechanism relies on the folding of mL45 inside the exit tunnel, forming two specific constriction sites that would limit helix formation of the nascent chain. A gap is formed between the exit and the membrane, making the newly synthesized proteins accessible. Our data elucidate the basis by which mitoribosomes interact with the OXA1L insertase to couple protein synthesis and membrane delivery.
线粒体核糖体（mitoribosomes）与线粒体内膜相连，以促进合成蛋白质的共翻译膜插入。我们报道了与插入酶氧化酶组装 1 样蛋白（OXA1L）结合的带有新生多肽的人线粒体核糖体的冷冻电镜结构，通过三个不同的接触点。OXA1L 的结合与线粒体核糖体大亚基的一系列构象变化相关，这些变化催化新合成多肽的递呈。该机制依赖于 mL45 在出口隧道内的折叠，形成两个特定的紧缩位点，限制新生链的螺旋形成。出口和膜之间形成一个间隙，使新合成的蛋白质能够进入。我们的数据阐明了线粒体核糖体与 OXA1L 插入酶相互作用以连接蛋白质合成和膜递呈的基础。
