Structural Basis for the Decoding Mechanism

The bacterial ribosome is a complex macromolecular machine that deciphers the genetic code with remarkable fidelity. During the elongation phase of protein synthesis, the ribosome selects aminoacyl-tRNAs as dictated by the canonical base pairing between the anticodon of the tRNA and the codon of the messenger RNA. The ribosome's participation in tRNA selection is active rather than passive, using conformational changes of conserved bases of 16S rRNA to directly monitor the geometry of codon-anticodon base pairing. The tRNA selection process is divided into an initial selection step and a subsequent proofreading step, with the utilization of two sequential steps increasing the discriminating power of the ribosome far beyond that which could be achieved based on the thermodynamics of codon-anticodon base pairing stability. The accuracy of decoding is impaired by a number of antibiotics and can be either increased or decreased by various mutations in either subunit of the ribosome, in elongation factor Tu, and in tRNA. In this chapter we will review our current understanding of various forces that determine the accuracy of decoding by the bacterial ribosome.