Mechanism of Membrane-tethered Mitochondrial Protein Synthesis

Overview

Journal Science

Specialty Science

Date 2021 Feb 19

PMID 33602856

Citations 68

Authors

Yuzuru Itoh

Juni Andrell

Austin Choi

Uwe Richter

Priyanka Maiti

Robert B Best

Antoni Barrientos

Brendan J Battersby

Alexey Amunts

Affiliations

Soon will be listed here.

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.

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