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Compensatory Evolution Reveals Functional Interactions between Ribosomal Proteins S12, L14 and L19
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
2007 (English)In: Journal of Molecular Biology, ISSN 0022-2836, E-ISSN 1089-8638, Vol. 366, no 1, 207-215 p.Article in journal (Refereed) Published
Abstract [en]

Certain mutations in S12, a ribosomal protein involved in translation elongation rate and translation accuracy, confer resistance to the arninoglycoside streptomycin. Previously we showed in Salmonella typhimurium that the fitness cost, i.e. reduced growth rate, due to the amino acid substitution K42N in S12 could be compensated by at least 35 different mutations located in the ribosomal proteins S4, S5 and L19. Here, we have characterized in vivo the fitness, translation speed and translation accuracy of four different L19 mutants. When separated from the resistance mutation located in S12, the three different compensatory amino acid substitutions in L19 at position 40 (Q40H, Q40L and Q40R) caused a decrease in fitness while the G104A change had no effect on bacterial growth. The rate of protein synthesis was unaffected or increased by the mutations at position 40 and the level of readthrough of a UGA nonsense codon was increased in vivo, indicating a loss of translational accuracy. The mutations in L19 increased sensitivity to aminoglycosides active at the A-site, further indicating a perturbation of the decoding step. These phenotypes are similar to those of the classical S4 and S5 ram (ribosomal ambiguity) mutants. By evolving low-fitness L19 mutants by serial passage, we showed that the fitness cost conferred by the L19 mutations could be compensated by additional mutations in the ribosomal protein L19 itself, in S12 and in L14, a protein located close to L19. Our results reveal a novel functional role for the 50 S ribosomal protein L19 during protein synthesis, supporting published structural data suggesting that the interaction of L14 and L19 with 16 S rRNA could influence function of the 30 S subunit. Moreover, our study demonstrates how compensatory fitness-evolution can be used to discover new molecular functions of ribosomal proteins.

Place, publisher, year, edition, pages
2007. Vol. 366, no 1, 207-215 p.
National Category
Medical and Health Sciences Biological Sciences
URN: urn:nbn:se:uu:diva-22338DOI: 10.1016/j.jmb.2006.11.047ISI: 000244161200017PubMedID: 17157877OAI: oai:DiVA.org:uu-22338DiVA: diva2:50111
Available from: 2007-01-16 Created: 2007-01-16 Last updated: 2011-06-30Bibliographically approved

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