Human GTPBP5 is involved in the late stage of mitoribosome large subunit assembly.

Autor:	Cipullo M; Department of Medical Biochemistry and Biophysics, Division of Molecular Metabolism, Karolinska Institutet, Solnavägen 9, 171 65 Solna, Sweden.; Max Planck Institute Biology of Ageing - Karolinska Institutet Laboratory, Karolinska Institutet, Stockholm, Sweden., Pearce SF; Department of Medical Biochemistry and Biophysics, Division of Molecular Metabolism, Karolinska Institutet, Solnavägen 9, 171 65 Solna, Sweden.; Max Planck Institute Biology of Ageing - Karolinska Institutet Laboratory, Karolinska Institutet, Stockholm, Sweden., Lopez Sanchez IG; Department of Medical Biochemistry and Biophysics, Division of Molecular Metabolism, Karolinska Institutet, Solnavägen 9, 171 65 Solna, Sweden.; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, 32 Gisborne Street, East Melbourne, 3002 Victoria, Australia., Gopalakrishna S; Department of Medical Biochemistry and Biophysics, Division of Molecular Metabolism, Karolinska Institutet, Solnavägen 9, 171 65 Solna, Sweden.; Max Planck Institute Biology of Ageing - Karolinska Institutet Laboratory, Karolinska Institutet, Stockholm, Sweden., Krüger A; Department of Medical Biochemistry and Biophysics, Division of Molecular Metabolism, Karolinska Institutet, Solnavägen 9, 171 65 Solna, Sweden.; Max Planck Institute Biology of Ageing - Karolinska Institutet Laboratory, Karolinska Institutet, Stockholm, Sweden., Schober F; Max Planck Institute Biology of Ageing - Karolinska Institutet Laboratory, Karolinska Institutet, Stockholm, Sweden.; Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Solna (L1:00), 171 76 Stockholm, Sweden., Busch JD; Department of Mitochondrial Biology, Max-Planck-Institute for Biology of Ageing, Joseph-Stelzmann-Str. 9b, 50931 Cologne, Germany., Li X; Proteomics Core Facility, Max-Planck-Institute for Biology of Ageing, Joseph-Stelzmann-Str. 9b, 50931 Cologne, Germany., Wredenberg A; Department of Medical Biochemistry and Biophysics, Division of Molecular Metabolism, Karolinska Institutet, Solnavägen 9, 171 65 Solna, Sweden.; Max Planck Institute Biology of Ageing - Karolinska Institutet Laboratory, Karolinska Institutet, Stockholm, Sweden., Atanassov I; Proteomics Core Facility, Max-Planck-Institute for Biology of Ageing, Joseph-Stelzmann-Str. 9b, 50931 Cologne, Germany., Rorbach J; Department of Medical Biochemistry and Biophysics, Division of Molecular Metabolism, Karolinska Institutet, Solnavägen 9, 171 65 Solna, Sweden.; Max Planck Institute Biology of Ageing - Karolinska Institutet Laboratory, Karolinska Institutet, Stockholm, Sweden.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2021 Jan 11; Vol. 49 (1), pp. 354-370.
DOI:	10.1093/nar/gkaa1131
Abstrakt:	Human mitoribosomes are macromolecular complexes essential for translation of 11 mitochondrial mRNAs. The large and the small mitoribosomal subunits undergo a multistep maturation process that requires the involvement of several factors. Among these factors, GTP-binding proteins (GTPBPs) play an important role as GTP hydrolysis can provide energy throughout the assembly stages. In bacteria, many GTPBPs are needed for the maturation of ribosome subunits and, of particular interest for this study, ObgE has been shown to assist in the 50S subunit assembly. Here, we characterize the role of a related human Obg-family member, GTPBP5. We show that GTPBP5 interacts specifically with the large mitoribosomal subunit (mt-LSU) proteins and several late-stage mitoribosome assembly factors, including MTERF4:NSUN4 complex, MRM2 methyltransferase, MALSU1 and MTG1. Interestingly, we find that interaction of GTPBP5 with the mt-LSU is compromised in the presence of a non-hydrolysable analogue of GTP, implying a different mechanism of action of this protein in contrast to that of other Obg-family GTPBPs. GTPBP5 ablation leads to severe impairment in the oxidative phosphorylation system, concurrent with a decrease in mitochondrial translation and reduced monosome formation. Overall, our data indicate an important role of GTPBP5 in mitochondrial function and suggest its involvement in the late-stage of mt-LSU maturation. (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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