. . . To encourage the growth of any science, the best thing we can do is to meet together in its interest, to discuss its problems, to criticize each other's work and, best of all, to provide means by which the better portion of it may be made known to the world. . . .
Henry A. Rowland, the first president of the American Physical Society
Biophysics
Title:
Molecular Architecture of a late 40S Ribosome Assembly Intermediate
Speaker:
Dr. Harish Vashisth, Department of Chemistry, University of Michigan, Ann Arbor, MI
Ribosomes are self-assembling macromolecular machines which catalyze the synthesis of proteins in all cells, and are made up of two subunits that differ in size due to varying ratio of RNA to proteins, the building blocks of the ribosomal subunits. Although significant structural details of the organization of mature ribosomes in prokaryotes and eukaryotes have been elucidated in the past decade, ribosome biogenesis and assembly processes are yet poorly understood. Ribosome assembly in eukaryotes requires at least 200 essential transiently associating assembly factor proteins that facilitate the RNA folding and recruitment of the ribosomal proteins.
In this talk, I will present our work on understanding the biogenesis of smaller eukaryotic ribosomal subunit (40S), where we have determined the structure of a late cytoplasmic 40S ribosome assembly intermediate from Saccharomyces Cerevisiae with the help of Cryo-electron microscopy and multi-scale molecular simulation techniques. We have collected maps of the immature 40S particles and its components at various resolutions, and apply molecular dynamics based flexible fitting (MDFF) to fit an initial atomic model into the Cryo-EM maps of immature 40S particles with minimal structural perturbation. We verify that the largest conformational change observed in RNA can be robustly generated with an independent technique called normal mode flexible fitting (NMFF). More importantly, we find that the pre-40s particles in addition to ribosomal RNA and proteins also contain 7 types of assembly factors, the joint activity of which blocks the translation initiation pathway in immature 40S subunits.
Undergraduates
