近日，瑞典斯德哥尔摩大学Alexey Amunts等研究人员合作揭示膜束缚的线粒体蛋白合成机理。这一研究成果于2021年2月19日发表在国际学术期刊《科学》上。

研究人员报道了具有新生多肽的人类线粒体核糖体冷冻电镜结构，其通过三个不同的接触位点与插入酶氧化酶组装体1样（OXA1L）蛋白结合。OXA1L绑定与线粒体核糖体大亚基的一系列构象变化相关，并催化新合成多肽的传递。该机制依赖于出口通道内的mL45折叠，从而形成两个特定的缩窄位点，这些位点会限制新生链的螺旋结构。出口和膜之间形成间隙，使新合成的蛋白质可及。

这些数据阐明了线粒体与OXA1L插入酶相互作用来耦合蛋白质合成和膜传递的基础。 

据了解，线粒体核糖体（mitoribosome）被拴在线粒体内膜上，从而促进合成蛋白的共翻译膜插入。

附：英文原文

Title: Mechanism of membrane-tethered mitochondrial protein synthesis

Author: Yuzuru Itoh, Juni Andréll, Austin Choi, Uwe Richter, Priyanka Maiti, Robert B. Best, Antoni Barrientos, Brendan J. Battersby, Alexey Amunts

Issue&Volume: 2021/02/19

Abstract: 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.

DOI: 10.1126/science.abe0763

Source: https://science.sciencemag.org/content/371/6531/846