Structural Insights into the Mechanism of Mitoribosomal Large Subunit Biogenesis
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Date
2020-08-20
Publication Type
Journal Article
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yes
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Abstract
In contrast to the bacterial translation machinery, mitoribosomes and mitochondrial translation factors are highly divergent in terms of composition and architecture. There is increasing evidence that the biogenesis of mitoribosomes is an intricate pathway, involving many assembly factors. To better understand this process, we investigated native assembly intermediates of the mitoribosomal large subunit from the human parasite Trypanosoma brucei using cryo-electron microscopy. We identify 28 assembly factors, 6 of which are homologous to bacterial and eukaryotic ribosome assembly factors. They interact with the partially folded rRNA by specifically recognizing functionally important regions such as the peptidyltransferase center. The architectural and compositional comparison of the assembly intermediates indicates a stepwise modular assembly process, during which the rRNA folds toward its mature state. During the process, several conserved GTPases and a helicase form highly intertwined interaction networks that stabilize distinct assembly intermediates. The presented structures provide general insights into mitoribosomal maturation. © 2020 Elsevier Inc.
The structures of two assembly intermediates of the Trypanosoma brucei mitoribosomal large subunit in combination with biochemical analysis provide insights into the stepwise mitoribosomal biogenesis process that involves numerous assembly factors functioning as enzymes or scaffold components. © 2020 Elsevier Inc.
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published
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Journal / series
Volume
79 (4)
Pages / Article No.
629 - 6440000
Publisher
Cell Press
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Edition / version
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Date collected
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Subject
Mitochondrial ribosome; Mitoribosome; Ribosome assembly; Ribosome biogenesis; Ribosomal maturation; Assembly factors; Trypanosoma brucei; Cryo-EM structure; Peptidyltransferase center; Ribosomal GTPases
Organisational unit
03556 - Ban, Nenad / Ban, Nenad
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Funding
163478 - Bonus of Excellence - Structural studies of complexes involved in ribosome assembly and translation initiation in yeast (SNF)