Cross-hypersensitivity effects of mutations in 23 S rRNA yield insight into aminoacyl-tRNA binding.
Halobacterium halobium cells contain one set of rRNA genes per genome. They have been used to characterize spontaneous mutants, carrying single nucleotide mutations in their rRNAs, that are resistant to different ribosomal antibiotics. Here we demonstrate that two different mutants that show resistance to thiostrepton, an inhibitor of the ribosomal GTPase-centre, are hypersensitive to amicetin, and other antibiotics, which act at the peptidyl transferase centre. Conversely, an amicetin-resistant mutant exhibits hypersensitivity to thiostrepton. A model is presented in which the two mutated sites, which are widely separated in the primary and secondary structure of 23 S rRNA, both participate in A-site binding of aminoacyl-tRNA.
Center for Pharmaceutical Biotechnology m/c 874, University of Illinois, Chicago 60612.
A S
AS
Mankin
I
I
Leviev
R A
RA
Garrett
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001483:Base Sequence; D004352:Drug Resistance, Microbial / Q000235:genetics*; D019617:Halobacterium salinarum / Q000235:genetics*; D008957:Models, Genetic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017354:Point Mutation; D011741:Pyrimidine Nucleosides / Q000494:pharmacology; D012338:RNA, Ribosomal, 23S; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism*; D013883:Thiostrepton / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D011741:Pyrimidine Nucleosides; D012338:RNA, Ribosomal, 23S; D012346:RNA, Transfer, Amino Acyl; C004413:amicetin; D013883:Thiostrepton