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Structure paper

TitleMechanism of membrane-tethered mitochondrial protein synthesis.
Journal, issue, pagesScience, Vol. 371, Issue 6531, Page 846-849, Year 2021
Publish dateFeb 19, 2021
AuthorsYuzuru Itoh / Juni Andréll / Austin Choi / Uwe Richter / Priyanka Maiti / Robert B Best / Antoni Barrientos / Brendan J Battersby / Alexey Amunts /
PubMed AbstractMitochondrial ribosomes (mitoribosomes) are tethered to the mitochondrial inner membrane to facilitate the cotranslational membrane insertion of the synthesized proteins. We report cryo-electron ...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.
External linksScience / PubMed:33602856 / PubMed Central
MethodsEM (single particle)
Resolution2.59 - 3.2 Å
Structure data

EMDB-11278, PDB-6zm5:
Human mitochondrial ribosome in complex with OXA1L, mRNA, A/A tRNA, P/P tRNA and nascent polypeptide
Method: EM (single particle) / Resolution: 2.89 Å

EMDB-11279, PDB-6zm6:
Human mitochondrial ribosome in complex with mRNA, A/A tRNA and P/P tRNA
Method: EM (single particle) / Resolution: 2.59 Å

EMDB-11280:
Human mitochondrial ribosome in complex with OXA1L, mRNA, A/A tRNA, P/P tRNA and nascent polypeptide, local-masked aligned on CP
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-11281:
Human mitochondrial ribosome in complex with OXA1L, mRNA, A/A tRNA, P/P tRNA and nascent polypeptide, local-masked aligned on L10-L7/L12-stalk
Method: EM (single particle) / Resolution: 3.16 Å

EMDB-11282:
Human mitochondrial ribosome in complex with OXA1L, mRNA, A/A tRNA, P/P tRNA and nascent polypeptide, local-masked aligned on SSU body
Method: EM (single particle) / Resolution: 3.03 Å

EMDB-11283:
Human mitochondrial ribosome in complex with OXA1L, mRNA, A/A tRNA, P/P tRNA and nascent polypeptide, local-masked aligned on SSU head
Method: EM (single particle) / Resolution: 3.07 Å

EMDB-11284:
Human mitochondrial ribosome in complex with mRNA, A/A tRNA and P/P tRNA, local-masked aligned on CP
Method: EM (single particle) / Resolution: 2.89 Å

EMDB-11285:
Human mitochondrial ribosome in complex with mRNA, A/A tRNA and P/P tRNA, local-masked aligned on L10-L7/L12-stalk
Method: EM (single particle) / Resolution: 2.89 Å

EMDB-11286:
Human mitochondrial ribosome in complex with mRNA, A/A tRNA and P/P tRNA, local-masked aligned on SSU body
Method: EM (single particle) / Resolution: 2.78 Å

EMDB-11287:
Human mitochondrial ribosome in complex with mRNA, A/A tRNA and P/P tRNA, local-masked aligned on SSU head.
Method: EM (single particle) / Resolution: 2.84 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-K:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-FES:
FE2/S2 (INORGANIC) CLUSTER / Iron–sulfur cluster

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM / Adenosine triphosphate

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM / Guanosine triphosphate

ChemComp-ALA:
ALANINE / Alanine

ChemComp-HOH:
WATER / Water

Source
  • homo sapiens (human)
KeywordsRIBOSOME / mitochondrion / translation / membrane insertion / translocon / peptidyl-tRNA / closed nascent-polypeptide tunnel

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