Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Structural basis of mitochondrial translation
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).ORCID iD: 0000-0003-2221-482X
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab). Karolinska Institutet, Sweden.ORCID iD: 0000-0003-4656-3362
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab). Karolinska Institutet, Sweden.ORCID iD: 0000-0002-5302-1740
Number of Authors: 42020 (English)In: eLIFE, E-ISSN 2050-084X, Vol. 9, article id e58362Article in journal (Refereed) Published
Abstract [en]

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 similar to 3.0 angstrom 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.

Place, publisher, year, edition, pages
2020. Vol. 9, article id e58362
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:su:diva-185337DOI: 10.7554/eLife.58362ISI: 000563031000001PubMedID: 32812867OAI: oai:DiVA.org:su-185337DiVA, id: diva2:1506659
Available from: 2020-12-03 Created: 2020-12-03 Last updated: 2023-03-16Bibliographically approved
In thesis
1. Structural investigation of human mitochondrial translation and off-target antibiotic binding
Open this publication in new window or tab >>Structural investigation of human mitochondrial translation and off-target antibiotic binding
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Human mitochondrial translation machinery has evolved to translate 13 mitochondrial mRNAs encoding components of the oxidative phosphorylation pathway responsible for ATP production. The structural basis of human mitochondrial translation is distinct from the canonical bacterial and cytosolic translation systems. Further, mutations affecting mitochondrial protein synthesis disrupt ATP production resulting in myopathies and neurodegenerative diseases. Structural studies have identified the core components of the human mitoribosome and some of its associated translation factors but several important aspects such as the role of mito-specific proteins in translation, rRNA modifications, composition of its ultrastructure including ions, small molecule co-factors, and solvent content, remain poorly understood. Importantly, several important antibiotics that target bacterial translation also affect mitochondrial translation, thereby causing adverse effects in patients. Understanding the mechanism of off-target antibiotic binding to the mitoribosome could help in designing better antibiotics. In this work, we use electron cryo-microscopy to determine the structures of the human mitoribosome in complex with ligands: mRNA/tRNA and translation activators such as LRPPRC-SLIRP. This allows us to explore the structural basis of mitochondrial translation, identifying the roles of mito-specific protein elements in tRNA and mRNA binding and recruitment (Papers 1 and 2). We determine a 2.2 Å resolution structure of the human mitoribosome and a 2.4 Å resolution structure of the mitoribosomal small subunit in complex with the tuberculosis drug, streptomycin. Together, the structures represent the most detailed and complete models for the human mitoribosome, revealing rRNA and protein modifications; several novel small molecule cofactors: 2Fe-2S clusters, polyamines and nucleotides and mechanisms of antibiotic binding (Papers 3 and 4).

Place, publisher, year, edition, pages
Stockholm: Department of Biochemistry and Biophysics, Stockholm University, 2023. p. 65
Keywords
Mitochondrial translation, mitoribosome, electron cryo-microscopy, LRPPRC-SLIRP, antibiotics, streptomycin
National Category
Structural Biology Biophysics Biochemistry and Molecular Biology
Research subject
Biophysics
Identifiers
urn:nbn:se:su:diva-215504 (URN)978-91-8014-240-3 (ISBN)978-91-8014-241-0 (ISBN)
Public defence
2023-04-24, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 14:00 (English)
Opponent
Supervisors
Available from: 2023-03-30 Created: 2023-03-16 Last updated: 2023-03-24Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Authority records

Aibara, ShintaroSingh, VivekAmunts, Alexey

Search in DiVA

By author/editor
Aibara, ShintaroSingh, VivekAmunts, Alexey
By organisation
Department of Biochemistry and BiophysicsScience for Life Laboratory (SciLifeLab)
In the same journal
eLIFE
Biological Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 134 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf