A molecular clamp ensures allosteric coordination of peptidyltransfer and ligand binding to the ribosomal A-site.
Although the ribosome is mainly comprised of rRNA and many of its critical functions occur through RNA-RNA interactions, distinct domains of ribosomal proteins also participate in switching the ribosome between different conformational/functional states. Prior studies demonstrated that two extended domains of ribosomal protein L3 form an allosteric switch between the pre- and post-translocational states. Missing was an explanation for how the movements of these domains are communicated among the ribosome's functional centers. Here, a third domain of L3 called the basic thumb, that protrudes roughly perpendicular from the W-finger and is nestled in the center of a cagelike structure formed by elements from three separate domains of the large subunit rRNA is investigated. Mutagenesis of basically charged amino acids of the basic thumb to alanines followed by detailed analyses suggests that it acts as a molecular clamp, playing a role in allosterically communicating the ribosome's tRNA occupancy status to the elongation factor binding region and the peptidyltransferase center, facilitating coordination of their functions through the elongation cycle. The observation that these mutations affected translational fidelity, virus propagation and cell growth demonstrates how small structural changes at the atomic scale can propagate outward to broadly impact the biology of cell.
Meskauskas
Arturas
A
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA. artmeska@umd.edu
Dinman
Jonathan D
JD
D000494:Allosteric Regulation; D001665:Binding Sites; D018965:Frameshifting, Ribosomal; D008024:Ligands; D008958:Models, Molecular; D009154:Mutation; D020652:Peptide Elongation Factor 2 / Q000378:metabolism; D010458:Peptidyl Transferases / Q000378:metabolism; D012335:RNA, Ribosomal / Q000737:chemistry; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins / Q000737:chemistry* / Q000235:genetics; D012270:Ribosomes / Q000737:chemistry* / Q000378:metabolism; D015003:Yeasts / Q000254:growth & development / Q000821:virology
D008024:Ligands; D020652:Peptide Elongation Factor 2; D012335:RNA, Ribosomal; D012346:RNA, Transfer, Amino Acyl; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins; C065039:RNA, ribosomal, 25S; D010458:Peptidyl Transferases