Title: Structures of the bacterial ribosome and the mechanism of translocation
The ribosome is the universally conserved cellular machine that translates the genetic code into proteins. Protein biosynthesis requires many large-scale rearrangements in the ribosome as each amino acid is added to a growing polypeptide chain. A key conformational change in the ribosome that is essential for translation is rotation of the small ribosomal subunit relative to the large subunit. Rotation of the ribosomal subunits occurs in all stages of translation–initiation, elongation, termination, and ribosome recycling–and is targeted by clinically useful antibiotics. In addition to rotation of the two ribosomal subunits, large-scale movements of the head domain of the small ribosomal subunit are thought to control the movement of mRNA and tRNAs as they traverse the three tRNA binding sites within the ribosome, a process termed translocation. As with subunit rotation, movement of the head domain is a target for clinically useful antibiotics. I will present structures of the 70S ribosome from Escherichia coli that reveal new aspects of the molecular basis for subunit rotation and movement of the head domain of the small subunit. In bacteria, the ribosome is targeted by numerous antibiotics, which affect many steps in protein synthesis. I will also present structures of the ribosome with antibiotics bound that shed light on how these compounds inhibit specific steps of the translocation mechanism.