@article{fe4076a4d53c4c7e991844f4ace22ecf,
title = "Mechanism of membrane-tethered mitochondrial protein synthesis",
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.",
author = "Yuzuru Itoh and Juni Andr{\'e}ll and Austin Choi and Uwe Richter and Priyanka Maiti and Best, {Robert B.} and Antoni Barrientos and Battersby, {Brendan J.} and Alexey Amunts",
note = "Funding Information: Funding: Swedish Foundation for Strategic Research (FFL15:0325), Ragnar S?derberg Foundation (M44/16), Cancerfonden (2017/1041), European Research Council (ERC-2018-StG-805230), Knut and Alice Wallenberg Foundation (2018.0080), The Academy of Finland (307431 and 314706 to B.J.B.), Sigrid Juselius Foundation (to B.J.B), NIH-R35 grant (GM118141 to A.B.), and MDA Research Grant (MDA-381828 to A.B.) supported this work. R.B.B. was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases of the NIH. This work used the computational resources of the NIH HPC Biowulf cluster (https://hpc.nih.gov). Y.I. was supported by H2020-MSCA-IF-2017 (799399-Itohribo). P.M. is the recipient of a postdoctoral fellowship from the American Heart Association (19POST34450174) Publisher Copyright: {\textcopyright} 2021 American Association for the Advancement of Science. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = feb,
day = "19",
doi = "10.1126/science.abe0763",
language = "English (US)",
volume = "371",
pages = "846--849",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6531",
}