Error-prone protein synthesis in parasites with the smallest eukaryotic genome
| Autor: | Mark J. Solomon, Darryl J. Pappin, Arthur Makarenko, James J. Becnel, Catherine Texier, Denis Ostapenko, Dieter Söll, Neil D. Sanscrainte, Sergey Melnikov, Keith Rivera |
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| Přispěvatelé: | National Research University of Information Technologies, Mechanics and Optics [St. Petersburg] (ITMO), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Department of Molecular Biophysics and Biochemistry-Yale (DMBB), Yale University [New Haven], Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
[SDV]Life Sciences [q-bio] 030106 microbiology [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology Genome Amino Acyl-tRNA Synthetases Fungal Proteins 03 medical and health sciences RNA Transfer Protein biosynthesis ComputingMilieux_MISCELLANEOUS Genetics Fungal protein Multidisciplinary Microsporida fungi Protein primary structure RNA Fungal biology.organism_classification 030104 developmental biology PNAS Plus Protein Biosynthesis Proteome Eukaryote Genome Fungal Leucine |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, 2018, 115 (27), pp.E6245-E6253. ⟨10.1073/pnas.1803208115⟩ Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2018, 115 (27), pp.E6245-E6253. ⟨10.1073/pnas.1803208115⟩ |
| ISSN: | 0027-8424 1091-6490 |
| Popis: | Microsporidia are parasitic fungi-like organisms that invade the interior of living cells and cause chronic disorders in a broad range of animals, including humans. These pathogens have the tiniest known genomes among eukaryotic species, for which they serve as a model for exploring the phenomenon of genome reduction in obligate intracellular parasites. Here we report a case study to show an apparent effect of overall genome reduction on the primary structure and activity of aminoacyl-tRNA synthetases, indispensable cellular proteins required for protein synthesis. We find that most microsporidian synthetases lack regulatory and eukaryote-specific appended domains and have a high degree of sequence variability in tRNA-binding and catalytic domains. In one synthetase, LeuRS, an apparent sequence degeneration annihilates the editing domain, a catalytic center responsible for the accurate selection of leucine for protein synthesis. Unlike accurate LeuRS synthetases from other eukaryotic species, microsporidian LeuRS is error-prone: apart from leucine, it occasionally uses its near-cognate substrates, such as norvaline, isoleucine, valine, and methionine. Mass spectrometry analysis of the microsporidium Vavraia culicis proteome reveals that nearly 6% of leucine residues are erroneously replaced by other amino acids. This remarkably high frequency of mistranslation is not limited to leucine codons and appears to be a general property of protein synthesis in microsporidian parasites. Taken together, our findings reveal that the microsporidian protein synthesis machinery is editing-deficient, and that the proteome of microsporidian parasites is more diverse than would be anticipated based on their genome sequences. |
| Databáze: | OpenAIRE |
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