Ribosomal protein L3: Gatekeeper to the a site

被引:56
作者
Meskauskas, Arturas [1 ]
Dinman, Jonathan D. [1 ]
机构
[1] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA
关键词
PEPTIDYL-TRANSFERASE CENTER; YEAST SACCHAROMYCES-CEREVISIAE; POKEWEED ANTIVIRAL PROTEIN; TRANSFER-RNA; PEPTIDYLTRANSFERASE ACTIVITY; TRICHODERMIN RESISTANCE; ACTIVE-ROLE; MUTANTS; SUBUNIT; BINDING;
D O I
10.1016/j.molcel.2007.02.015
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
Ribosomal protein L3 (1-3) is an essential and indispensable component for formation of the peptidyltransferase center. Atomic resolution ribosome structures reveal two extensions of L3 protruding deep into the core of the large subunit. The central extension of L3 in Saccharomyces cerevisiae was investigated using a combination of molecular genetic, biochemical, chemical probing, and molecular modeling methods. A reciprocal relationship between ribosomal affinity for eEF-1 A stimulated binding of aa-tRNA and for eEF2 suggests that the central extension of L3 may function as an allosteric switch in coordinating binding of the elongation factors. Opening of the aa-tRNA accommodation corridor promoted resistance to the A site-specific translational inhibitor anisomycin, suggesting a competitive model for anisomycin resistance. These changes were also found to inhibit peptidyltransferase activity, stimulating programmed -1 ribosomal frameshifting and promoting virus propagation defects. These studies provide a basis for deeper insight into rational design of small molecule antiviral therapeutics.
引用
收藏
页码:877 / 888
页数:12
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