Multiple defects in translation associated with altered ribosomal protein L4.
The ribosomal proteins L4 and L22 form part of the peptide exit tunnel in the large ribosomal subunit. In Escherichia coli, alterations in either of these proteins can confer resistance to the macrolide antibiotic, erythromycin. The structures of the 30S as well as the 50S subunits from each antibiotic resistant mutant differ from wild type in distinct ways and L4 mutant ribosomes have decreased peptide bond-forming activity. Our analyses of the decoding properties of both mutants show that ribosomes carrying the altered L4 protein support increased levels of frameshifting, missense decoding and readthrough of stop codons during the elongation phase of protein synthesis and stimulate utilization of non-AUG codons and mutant initiator tRNAs at initiation. L4 mutant ribosomes are also altered in their interactions with a range of 30S-targeted antibiotics. In contrast, the L22 mutant is relatively unaffected in both decoding activities and antibiotic interactions. These results suggest that mutations in the large subunit protein L4 not only alter the structure of the 50S subunit, but upon subunit association, also affect the structure and function of the 30S subunit.
O'Connor
Michael
M
School of Biological Sciences, University of Missouri-Kansas City, 5007 Rockhill Road, Kansas City, MO 64110, USA. oconnormi@umkc.edu
Gregory
Steven T
ST
Dahlberg
Albert E
AE
D003062:Codon; D018388:Codon, Terminator; D004917:Erythromycin / Q000494:pharmacology; D004926:Escherichia coli / Q000235:genetics; D018965:Frameshifting, Ribosomal; D009154:Mutation; D020125:Mutation, Missense; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000737:chemistry; D012358:RNA, Transfer, Met / Q000378:metabolism; D012269:Ribosomal Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D012270:Ribosomes / Q000187:drug effects / Q000235:genetics*
D003062:Codon; D018388:Codon, Terminator; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D012358:RNA, Transfer, Met; D012269:Ribosomal Proteins; C056368:ribosomal protein L4; D004917:Erythromycin