Ribosomal protein L3: gatekeeper to the A site.
Ribosomal protein L3 (L3) 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-1A 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.
Meskauskas
Arturas
A
Department of Cell Biology and Molecular Genetics, University of Maryland, Microbiology Building, Room 2135, College Park, MD 20742, USA. artmeska@wam.umd.edu
Dinman
Jonathan D
JD
D001483:Base Sequence; D001665:Binding Sites; D004926:Escherichia coli / Q000235:genetics; D005784:Gene Amplification; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D012335:RNA, Ribosomal / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins / Q000737:chemistry* / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism
D012335:RNA, Ribosomal; C065096:RNA, ribosomal, 26S; D011994:Recombinant Proteins; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins; D014364:Tryptophan