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Structure paper

TitleStructural basis of TACO1-mediated efficient mitochondrial translation.
Journal, issue, pagesNat Commun, Year 2026
Publish dateFeb 9, 2026
AuthorsShuhui Wang / Michele Brischigliaro / Yuekang Zhang / Chunxiang Wu / Wei Zheng / Antoni Barrientos / Yong Xiong /
PubMed AbstractTranslation elongation is a universally conserved step in protein synthesis, relying on elongation factors that engage the ribosomal L7/L12 stalk to mediate aminoacyl-tRNA delivery, accommodation, ...Translation elongation is a universally conserved step in protein synthesis, relying on elongation factors that engage the ribosomal L7/L12 stalk to mediate aminoacyl-tRNA delivery, accommodation, and ribosomal translocation. Using in organello cryo-electron microscopy, we reveal how the mitochondrial translation accelerator TACO1 promotes efficient elongation on human mitoribosomes. TACO1 binds the mitoribosomal region typically bound by elongation factor Tu (mtEF-Tu), bridging the large and small subunits via contacts with 16S rRNA, bL12m, A-site tRNA, and uS12m. While active throughout elongation, TACO1 is especially critical when translating polyproline motifs. Its absence prolongs mtEF-Tu residence in A/T states, causes persistent mitoribosomal stalling and premature subunit dissociation. Structural analyses indicate that TACO1 competes with mtEF-Tu for mitoribosome binding, stabilizes A-site tRNA, and enhances peptidyl transfer through a mechanism distinct from EF-P and eIF5A. These findings suggest that bacterial TACO1 orthologs may serve analogous roles, highlighting an evolutionarily conserved strategy for maintaining elongation efficiency during challenging translation events.
External linksNat Commun / PubMed:41663403
MethodsEM (single particle)
Resolution2.46 - 3.34 Å
Structure data

EMDB-70592, PDB-9olf:
Membrane-associated human mitoribosome in complex with TACO1
Method: EM (single particle) / Resolution: 2.46 Å

EMDB-70620: In situ mitoribosome focused on the mtSSU
Method: EM (single particle) / Resolution: 2.65 Å

EMDB-70621: Consensus map of the mitoribosome complexed with TACO1
Method: EM (single particle) / Resolution: 2.48 Å

EMDB-71797, PDB-9pr4:
In Situ Structure of the Human Mitochondrial Large Subunit 39S in Complex with TACO1
Method: EM (single particle) / Resolution: 2.77 Å

EMDB-71802, PDB-9pra:
In Situ Structure of the Human Mitoribosome Large Subunit 39S in Complex with EF-Tu
Method: EM (single particle) / Resolution: 2.83 Å

EMDB-71809, PDB-9prd:
In situ structure of the human mitoribosome in the P state from TACO1-knockout cells
Method: EM (single particle) / Resolution: 3.31 Å

EMDB-71811, PDB-9prq:
In situ structure of human mitoribosome in the A/T-P state from TACO1-knockout cells
Method: EM (single particle) / Resolution: 3.34 Å

EMDB-71815, PDB-9prx:
In situ structure of the human mitoribosome in the A-P state from TACO1-knockout cells
Method: EM (single particle) / Resolution: 3.23 Å

EMDB-71818, PDB-9ps0:
In situ structure of the human mitoribosome in the A/P-P/E state from TACO1-knockout cells
Method: EM (single particle) / Resolution: 3.29 Å

EMDB-71825, PDB-9ps7:
In situ structure of the human mitoribosome in the A/T-P-E state from TACO1-knockout cells
Method: EM (single particle) / Resolution: 3.08 Å

EMDB-71828, PDB-9psi:
In situ structure of the human mitoribosome in the A-P-E state from TACO1-knockout cells
Method: EM (single particle) / Resolution: 3.12 Å

EMDB-71829, PDB-9psm:
In situ structure of the human mitoribosome in the A/P-P/E state
Method: EM (single particle) / Resolution: 2.98 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-SPD:
SPERMIDINE

ChemComp-MG:
Unknown entry

ChemComp-PUT:
1,4-DIAMINOBUTANE

ChemComp-K:
Unknown entry

ChemComp-SPM:
SPERMINE

ChemComp-NAD:
NICOTINAMIDE-ADENINE-DINUCLEOTIDE / NAD*YM

ChemComp-FES:
FE2/S2 (INORGANIC) CLUSTER

ChemComp-GDP:
GUANOSINE-5'-DIPHOSPHATE / GDP, energy-carrying molecule*YM

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

ChemComp-VAL:
VALINE

Source
  • homo sapiens (human)
KeywordsRIBOSOME / mitochondria / mitoribosome / inner membrane / mitochondrial ribosome

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