Mitochondrial translation factors of Trypanosoma brucei: elongation factor-Tu has a unique subdomain that is essential for its function

0420949 - BC 2014 RIV GB eng J - Článek v odborném periodiku
Cristodero, M. - Mani, J. - Oeljeklaus, S. - Aeberhard, L. - Hashimi, Hassan - Ramrath, D.J.F. - Lukeš, Julius - Warscheid, B. - Schneider, A.
Mitochondrial translation factors of Trypanosoma brucei: elongation factor-Tu has a unique subdomain that is essential for its function.
Molecular Microbiology. Roč. 90, č. 4 (2013), s. 744-755. ISSN 0950-382X. E-ISSN 1365-2958
Grant CEP: GA ČR GAP305/12/2261
Institucionální podpora: RVO:60077344
Klíčová slova: mitochondrial translation * Trypanosoma brucei * EF-Tu
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 5.026, rok: 2013

Mitochondrial translation in the parasitic protozoan Trypanosoma brucei relies on imported eukaryotic-type tRNAs as well as on bacterial-type ribosomes that have the shortest known rRNAs. Here we have identified the mitochondrial translation elongation factors EF-Tu, EF-Ts, EF-G1 and release factor RF1 of trypanosomatids and show that their ablation impairs growth and oxidative phosphorylation. In vivo labelling experiments and a SILAC-based analysis of the global proteomic changes induced by EF-Tu RNAi directly link EF-Tu to mitochondrial translation. Moreover, EF-Tu RNAi reveals downregulation of many nuclear encoded subunits of cytochrome oxidase as well as of components of the bc1-complex, whereas most cytosolic ribosomal proteins were upregulated. Interestingly, T.brucei EF-Tu has a 30-amino-acid-long, highly charged subdomain, which is unique to trypanosomatids. A combination of RNAi and complementation experiments shows that this subdomain is essential for EF-Tu function, but that it can be replaced by a similar sequence found in eukaryotic EF-1a, the cytosolic counterpart of EF-Tu. A recent cryo-electron microscopy study revealed that trypanosomatid mitochondrial ribosomes have a unique intersubunit space that likely harbours the EF-Tu binding site. These findings suggest that the trypanosomatid-specific EF-Tu subdomain serves as an adaption for binding to these unusual mitochondrial ribosomes.
Trvalý link: http://hdl.handle.net/11104/0227477