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Structure paper

TitleStructural basis of mitochondrial translation.
Journal, issue, pagesElife, Vol. 9, Year 2020
Publish dateAug 19, 2020
AuthorsShintaro Aibara / Vivek Singh / Angelika Modelska / Alexey Amunts /
PubMed AbstractTranslation of mitochondrial messenger RNA (mt-mRNA) is performed by distinct mitoribosomes comprising at least 36 mitochondria-specific proteins. How these mitoribosomal proteins assist in the ...Translation of mitochondrial messenger RNA (mt-mRNA) is performed by distinct mitoribosomes comprising at least 36 mitochondria-specific proteins. How these mitoribosomal proteins assist in the binding of mt-mRNA and to what extent they are involved in the translocation of transfer RNA (mt-tRNA) is unclear. To visualize the process of translation in human mitochondria, we report ~3.0 Å resolution structure of the human mitoribosome, including the L7/L12 stalk, and eight structures of its functional complexes with mt-mRNA, mt-tRNAs, recycling factor and additional trans factors. The study reveals a transacting protein module LRPPRC-SLIRP that delivers mt-mRNA to the mitoribosomal small subunit through a dedicated platform formed by the mitochondria-specific protein mS39. Mitoribosomal proteins of the large subunit mL40, mL48, and mL64 coordinate translocation of mt-tRNA. The comparison between those structures shows dynamic interactions between the mitoribosome and its ligands, suggesting a sequential mechanism of conformational changes.
External linksElife / PubMed:32812867 / PubMed Central
MethodsEM (single particle)
Resolution3.5 - 5.0 Å
Structure data

EMDB-11390, PDB-6zs9:
Human mitochondrial ribosome in complex with ribosome recycling factor
Method: EM (single particle) / Resolution: 4.0 Å

EMDB-11391, PDB-6zsa:
Human mitochondrial ribosome bound to mRNA, A-site tRNA and P-site tRNA
Method: EM (single particle) / Resolution: 4.0 Å

EMDB-11392, PDB-6zsb:
Human mitochondrial ribosome in complex with mRNA and P-site tRNA
Method: EM (single particle) / Resolution: 4.5 Å

EMDB-11393, PDB-6zsc:
Human mitochondrial ribosome in complex with E-site tRNA
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-11394, PDB-6zsd:
Human mitochondrial ribosome in complex with mRNA, P-site tRNA and E-site tRNA
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-11395, PDB-6zse:
Human mitochondrial ribosome in complex with mRNA, A/P-tRNA and P/E-tRNA
Method: EM (single particle) / Resolution: 5.0 Å

EMDB-11397, PDB-6zsg:
Human mitochondrial ribosome in complex with mRNA, A-site tRNA, P-site tRNA and E-site tRNA
Method: EM (single particle) / Resolution: 4.0 Å

EMDB-12877, PDB-7og4:
Human mitochondrial ribosome in complex with P/E-tRNA
Method: EM (single particle) / Resolution: 3.8 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-MG:
Unknown entry

ChemComp-DOL:
5-(2-DIETHYLAMINO-ETHANESULFONYL)-21-HYDROXY-10-ISOPROPYL-11,19-DIMETHYL-9,26-DIOXA-3,15,28-TRIAZA-TRICYCLO[23.2.1.00,255]OCTACOSA-1(27),12,17,19,25(28)-PENTAENE-2,8,14,23-TETRAONE / antibiotic*YM / Dalfopristin

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

ChemComp-H8Q:
~{N}-[(3~{S},6~{R},12~{R},15~{S},16~{S},19~{S},22~{S},25~{S})-25-[[(3~{S})-1-azabicyclo[2.2.2]octan-3-yl]sulfanylmethyl]-3-[[4-(dimethylamino)phenyl]methyl]-12-ethyl-4,16-dimethyl-2,5,11,14,18,21,24-heptakis(oxidanylidene)-19-phenyl-17-oxa-1,4,10,13,20-pentazatricyclo[20.4.0.0^{6,10}]hexacosan-15-yl]-3-oxidanyl-pyridine-2-carboxamide / antibiotic*YM / Quinupristin

Source
  • homo sapiens (human)
  • synthetic construct (others)
  • Human (human)
KeywordsTRANSLATION / Mitochondria / Ribosome / mRNA / tRNA

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