rRNA mutants in the yeast peptidyltransferase center reveal allosteric information networks and mechanisms of drug resistance

被引:33
作者
Rakauskaite, Rasa [1 ]
Dinman, Jonathan D. [1 ]
机构
[1] Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA
关键词
D O I
10.1093/nar/gkm1179
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
To ensure accurate and rapid protein synthesis, nearby and distantly located functional regions of the ribosome must dynamically communicate and coordinate with one another through a series of information exchange networks. The ribosome is 2/3 rRNA and information should pass mostly through this medium. Here, two viable mutants located in the peptidyltransferase center (PTC) of yeast ribosomes were created using a yeast genetic system that enables stable production of ribosomes containing only mutant rRNAs. The specific mutants were C2820U (Escherichia coli C2452) and 2922C (E. coli U2554). Biochemical and genetic analyses of these mutants suggest that they may trap the PTC in the open or aa-tRNA bound conformation, decreasing peptidyl-tRNA binding. We suggest that these structural changes are manifested at the biological level by affecting large ribosomal subunit biogenesis, ribosomal subunit joining during initiation, susceptibility/resistance to peptidyltransferase inhibitors, and the ability of ribosomes to properly decode termination codons. These studies also add to our understanding of how information is transmitted both locally and over long distances through allosteric networks of rRNArRNA and rRNAprotein interactions.
引用
收藏
页码:1497 / 1507
页数:11
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