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An Arc of Unpaired "Hinge Bases" Facilitates Information Exchange among Functional Centers of the Ribosome

Department of Cell Biology and Molecular Genetics, University of Maryland, 2135 Microbiology Building, College Park, Maryland 20742

Received 18 July 2006/ Returned for modification 28 August 2006/ Accepted 11 September 2006

Information must be shared and functions coordinated among the spatially distinct functional centers of the ribosome. To address these issues, a yeast-based genetic system enabling generation of stable strains expressing only mutant forms of rRNA was devised. The B1a bridge (helix 38) has been implicated in the subtle modulation of numerous ribosomal functions. Base-specific mutations were introduced into helix 38 at sites affecting the B1a bridge and where it contacts the aminoacyl-tRNA (aa-tRNA) D-loop. Both sets of mutants promoted increased affinities for aa-tRNA but had different effects in their responses to two A-site-specific drugs and on suppression nonsense codons. Structural analyses revealed an arc of nucleotides in 25S rRNA that link the B1a bridge, the peptidyltransferase center, the GTPase-associated center, and the sarcin/ricin loop. We propose that a series of regularly spaced "hinge bases" provide fulcrums around which rigid helices can reorient themselves depending on the occupancy status of the A-site.

Published ahead of print on 25 September 2006.

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