Structural basis of TACO1 function in mitochondrial translation elongation

Abstract

Protein synthesis depends on specialized regulatory factors to overcome difficult-to-translate sequences during elongation that cause ribosomal stalling. In human mitochondria, this function is carried out by TACO1 (Translation activator of COX1). Here, we report the cryo-electron microscopy structure of human TACO1 bound to the mitoribosome, revealing its mechanistic role as a dedicated elongation regulator. Unlike the prokaryotic elongation factor EF-P and the eukaryotic eIF5A, which bind the ribosomal E site and stabilize P-site tRNA to facilitate peptide bond formation, TACO1 adopts a distinct strategy. It binds near the A site, closely interacting with the Sarcin Ricin loop and the L7/L12 stalk, similar to general translation elongation factors, such as EF-Tumt and mtEF-G1mt, and contacts the A-site tRNA. Using AlphaFold analysis and molecular dynamics simulations, we further show how a series of conformational changes allow its N-terminal domain to reorient and transiently engage with the A-site tRNA via a conserved and functionally critical basic amino acid patch. The bacterial homolog of TACO1, namely YebC2, shares the structural features required for its function. Overall, we present an evolutionarily conserved mechanism employed by TACO1 to enhance mitochondrial translation efficiency.

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BibTeX RIS

BibTeX

@article{singh2026structural,
  title = {{Structural basis of TACO1 function in mitochondrial translation elongation}},
  author = {Vivek Singh and Raven Gallenstein and George Wanes and Dmitri Igorevich Shiriaev and Evgeniia Shcherbinina and Shreekara Gopalakrishna and Kuerbannisha Amahong and Udayan Mohanty and Aishe A. Sarshad and Paul C. Whitford and Anas Khawaja and Joanna Rorbach},
  journal = {Nature Communications},
  year = {2026},
  month = oct,
  doi = {10.1038/s41467-026-78692-6},
  url = {https://www.nature.com/articles/s41467-026-78692-6},
  note = {CC BY 4.0},
}

RIS

TY  - JOUR
TI  - Structural basis of TACO1 function in mitochondrial translation elongation
AU  - Vivek Singh
AU  - Raven Gallenstein
AU  - George Wanes
AU  - Dmitri Igorevich Shiriaev
AU  - Evgeniia Shcherbinina
AU  - Shreekara Gopalakrishna
AU  - Kuerbannisha Amahong
AU  - Udayan Mohanty
AU  - Aishe A. Sarshad
AU  - Paul C. Whitford
AU  - Anas Khawaja
AU  - Joanna Rorbach
PY  - 2026
DA  - 2026/10/21
JO  - Nature Communications
DO  - 10.1038/s41467-026-78692-6
UR  - https://www.nature.com/articles/s41467-026-78692-6
AB  - Protein synthesis depends on specialized regulatory factors to overcome difficult-to-translate sequences during elongation that cause ribosomal stalling. In human mitochondria, this function is carried out by TACO1 (Translation activator of COX1). Here, we report the cryo-electron microscopy structure of human TACO1 bound to the mitoribosome, revealing its mechanistic role as a dedicated elongation regulator. Unlike the prokaryotic elongation factor EF-P and the eukaryotic eIF5A, which bind the ribosomal E site and stabilize P-site tRNA to facilitate peptide bond formation, TACO1 adopts a distinct strategy. It binds near the A site, closely interacting with the Sarcin Ricin loop and the L7/L12 stalk, similar to general translation elongation factors, such as EF-Tumt and mtEF-G1mt, and contacts the A-site tRNA. Using AlphaFold analysis and molecular dynamics simulations, we further show how a series of conformational changes allow its N-terminal domain to reorient and transiently engage with the A-site tRNA via a conserved and functionally critical basic amino acid patch. The bacterial homolog of TACO1, namely YebC2, shares the structural features required for its function. Overall, we present an evolutionarily conserved mechanism employed by TACO1 to enhance mitochondrial translation efficiency.
SN  - 2041-1723
ER  -

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