Mitoribosome structure with cofactors and modifications reveals mechanism of ligand binding and interactions with L1 stalk

Vivek Singh, Yuzuru Itoh, Samuel Del’Olio, Asem Hassan, Andreas Naschberger, Rasmus Kock Flygaard, Yuko Nobe, Keiichi Izumikawa, Shintaro Aibara, Juni Andréll, Paul C. Whitford, Antoni Barrientos, Masato Taoka and Alexey Amunts ()
Additional contact information
Vivek Singh: Stockholm University
Yuzuru Itoh: Stockholm University
Samuel Del’Olio: University of Miami Miller School of Medicine
Asem Hassan: Northeastern University
Andreas Naschberger: Stockholm University
Rasmus Kock Flygaard: Aarhus University
Yuko Nobe: Tokyo Metropolitan University
Keiichi Izumikawa: Meiji Pharmaceutical University
Shintaro Aibara: Stockholm University
Juni Andréll: Karolinska Institutet
Paul C. Whitford: Northeastern University
Antoni Barrientos: University of Miami Miller School of Medicine
Masato Taoka: Tokyo Metropolitan University
Alexey Amunts: Stockholm University

Nature Communications, 2024, vol. 15, issue 1, 1-22

Abstract: Abstract The mitoribosome translates mitochondrial mRNAs and regulates energy conversion that is a signature of aerobic life forms. We present a 2.2 Å resolution structure of human mitoribosome together with validated mitoribosomal RNA (rRNA) modifications, including aminoacylated CP-tRNAVal. The structure shows how mitoribosomal proteins stabilise binding of mRNA and tRNA helping to align it in the decoding center, whereas the GDP-bound mS29 stabilizes intersubunit communication. Comparison between different states, with respect to tRNA position, allowed us to characterize a non-canonical L1 stalk, and molecular dynamics simulations revealed how it facilitates tRNA transitions in a way that does not require interactions with rRNA. We also report functionally important polyamines that are depleted when cells are subjected to an antibiotic treatment. The structural, biochemical, and computational data illuminate the principal functional components of the translation mechanism in mitochondria and provide a description of the structure and function of the human mitoribosome.

Date: 2024
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DOI: 10.1038/s41467-024-48163-x

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