Mutations in domain II of 23 S rRNA facilitate translation of a 23 S rRNA-encoded pentapeptide conferring erythromycin resistance

被引:25
作者
Dam, M
Douthwaite, S
Tenson, T
Mankin, AS
机构
[1] ODENSE UNIV,DEPT MOLEC BIOL,DK-5230 ODENSE M,DENMARK
[2] UNIV ILLINOIS,CTR PHARMACEUT BIOTECHNOL,CHICAGO,IL 60607
[3] TARTU STATE UNIV,INST MOLEC & CELLULAR BIOL,TARTU 202400,ESTONIA
关键词
ribosome; rRNA; erythromycin; translation; drug resistance; RIBOSOMAL-RNA; REGION;
D O I
10.1006/jmbi.1996.0296
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mutations in domain II of Escherichia coli 23 S rRNA that cause resistance to erythromycin do so in a manner fundamentally different from mutations at the drug binding site in domain V of the 23 S rRNA. The domain II mutations are located in a hairpin structure between nucleotides 1198 and 1247. This is close to a short open reading frame in the 23 S rRNA that encodes a pentapeptide (E-peptide) whose expression in vivo renders cells resistant to erythromycin. Therefore, a possible mechanism of resistance caused by domain II mutations may be related to an increased expression of the E-peptide. To test this hypothesis, a range of point mutations was generated in domain II of 23 S rRNA in the vicinity of the E-peptide open reading frame. We find a correlation between erythromycin resistance of the mutant clones and increased accessibility of the ribosome binding site of the E-peptide gene. Furthermore, the erythromycin resistance determinant in the mutants was shown to be confined to a small 23 S rRNA segment containing the coding region and the ribosome binding site of the E-peptide open reading frame. It thus appears that the domain II mutations mediate erythromycin resistance by increasing expression of the 23 S rRNA-encoded E-peptide. (C) 1996 Academic Press Limited.
引用
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页码:1 / 6
页数:6
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