The Conformational Dynamics of eIF5B During Ribosomal Subunit Joining

PROJECT NARRATIVE Translation initiation, which requires the action of over a dozen initiation factors, is the rate-limiting step in the process of protein synthesis that establishes the frame in which the messenger RNA will be translated and that is one of the major checkpoints that is directly targeted during cellular stress and disease. Ribosomal initiation complexes undergo intricate conformational rearrangements upon initiation factor binding, and dysregulation of these conformational changes often underlie the onset of cellular stress and disease. This application proposes an investigation of the compositional and conformational dynamics of eukaryotic translation initiation complexes during the ribosomal subunit joining step of the initiation pathway that forms the final point of regulation during translation initiation.