Gali Prag
Tel Aviv University, Israel
Title: Bacterial genetics and structural biology for decoding the ubiquitin code
Biography
Biography: Gali Prag
Abstract
Ubiquitin (Ub)-signals virtually regulate all cellular pathways. However, two major challenges impede our ability to identify and characterize associations within ubiquitylation cascades: Ubiquitylation cascades are multiplex, i.e., few E1s, dozens E2s and hundreds of E3s ubiquitylate thousands of substrates. Moreover, many substrates possess more than one cognate E3-ligase. About a hundred deubiquitylases rapidly and efficiently reverse the ubiquitylation. To circumvent these limitations we took an integrating biology approach including structural based in silico search, bacterial genetics, biochemical, biophysicals and X-ray crystallography to establish a productive interdisciplinary research. A novel bacterial genetic selection system for ubiquitylation and its utilization in identifying and characterizing new E3s, Ub-receptors and ubiquitylation substrates will be presented. Using bacterial expression of a functional ubiquitylation apparatus we purified and crystallized and determined the structure of an ubiquitylated-Ub-receptor for the first time. We took a multidisciplinary approach and uncovered a novel UBD within this receptor. A surprising function of the Ub-receptor ubiquitylation will be presented. As the findings derived from the genetic selection system we developed and the crystal structure of ubiquitylated-ubiquitin-receptor are still under review so I will share the full result and discussion at presentation time.
