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; Alexey Amunts

doi:10.1038/s41467-024-48163-x

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, Alexey Amunts^*

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

6 Citationer (Scopus)

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-tRNA^Val. 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.

Originalsprog	Engelsk
Artikelnummer	4272
Tidsskrift	Nature Communications
Vol/bind	15
Nummer	1
ISSN	2041-1723
DOI	https://doi.org/10.1038/s41467-024-48163-x
Status	Udgivet - 20 maj 2024

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Singh, V., Itoh, Y., Del’Olio, S., Hassan, A., Naschberger, A., Flygaard, R. K., Nobe, Y., Izumikawa, K., Aibara, S., Andréll, J., Whitford, P. C., Barrientos, A., Taoka, M., & Amunts, A. (2024). Mitoribosome structure with cofactors and modifications reveals mechanism of ligand binding and interactions with L1 stalk. Nature Communications, 15(1), Artikel 4272. https://doi.org/10.1038/s41467-024-48163-x

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title = "Mitoribosome structure with cofactors and modifications reveals mechanism of ligand binding and interactions with L1 stalk",

abstract = "The mitoribosome translates mitochondrial mRNAs and regulates energy conversion that is a signature of aerobic life forms. We present a 2.2 {\AA} 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.",

author = "Vivek Singh and Yuzuru Itoh and Samuel Del{\textquoteright}Olio and Asem Hassan and Andreas Naschberger and Flygaard, {Rasmus Kock} and Yuko Nobe and Keiichi Izumikawa and Shintaro Aibara and Juni Andr{\'e}ll and Whitford, {Paul C.} and Antoni Barrientos and Masato Taoka and Alexey Amunts",

year = "2024",

month = may,

day = "20",

doi = "10.1038/s41467-024-48163-x",

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volume = "15",

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Singh, V, Itoh, Y, Del’Olio, S, Hassan, A, Naschberger, A, Flygaard, RK, Nobe, Y, Izumikawa, K, Aibara, S, Andréll, J, Whitford, PC, Barrientos, A, Taoka, M & Amunts, A 2024, 'Mitoribosome structure with cofactors and modifications reveals mechanism of ligand binding and interactions with L1 stalk', Nature Communications, bind 15, nr. 1, 4272. https://doi.org/10.1038/s41467-024-48163-x

Mitoribosome structure with cofactors and modifications reveals mechanism of ligand binding and interactions with L1 stalk. / Singh, Vivek; Itoh, Yuzuru; Del’Olio, Samuel et al.
I: Nature Communications, Bind 15, Nr. 1, 4272, 20.05.2024.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - Mitoribosome structure with cofactors and modifications reveals mechanism of ligand binding and interactions with L1 stalk

AU - Singh, Vivek

AU - Itoh, Yuzuru

AU - Del’Olio, Samuel

AU - Hassan, Asem

AU - Naschberger, Andreas

AU - Flygaard, Rasmus Kock

AU - Nobe, Yuko

AU - Izumikawa, Keiichi

AU - Aibara, Shintaro

AU - Andréll, Juni

AU - Whitford, Paul C.

AU - Barrientos, Antoni

AU - Taoka, Masato

AU - Amunts, Alexey

PY - 2024/5/20

Y1 - 2024/5/20

N2 - 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.

AB - 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.

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JO - Nature Communications

JF - Nature Communications

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

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