Wednesday January 23, 2013
“Cryo-EM of the Eukaryotic Ribosome: what can we learn on the regulation of translation?”
Amedee des Georges, Joachim Frank Lab, HHMI – Columbia University
In bacteria, protein expression is mainly regulated at the level of transcription. With their increased complexity, Eukaryotes have evolved more sophisticated ways to control levels and localization of proteins in the cell, and this is accomplished in part by a much more elaborate regulation of translation.
During translation initiation, bacterial 30S ribosomal subunits bind to mRNA via the Shine-Dalgarno interaction, placing the initiation codon directly into the P-site, primed for the subsequent elongation stage. In contrast, eukaryotic 40S ribosomes select the initiation codon by scanning the mRNA 5’UTR. Attachment to the 40S, scanning and recognition of the AUG start codon require many factors, all of which are opportunities for regulation.
I will describe recent advances that we have made at the structural level regarding this aspect of translation, which until now has been elusive in Eukaryotes. These advances may lead to potential drug targets against deadly parasites such as Trypanosoma Brucei, the parasite responsible for the sleeping sickness.