Mechanism of membrane-tethered mitochondrial protein synthesis.

Itoh Y, Andréll J, Choi A, Richter U, Maiti P, Best RB, Barrientos A, Battersby BJ, Amunts A

Science (New York, N.Y.) 371 (6531) 846-849 [2021-02-19; online 2021-02-20]

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.

Alexey Amunts

SciLifeLab Fellow

PubMed 33602856

DOI 10.1126/science.abe0763

Crossref 10.1126/science.abe0763

mid: EMS117578
pmc: PMC7610362
pii: 371/6531/846

Publications 9.5.0