Structural insights into the ubiquitin/SUMO conjugation and deconjugation pathways. Structural analysis of human RNases involved in host defense

Post-translational protein modification by ubiquitin or ubiquitin-like modifiers (Ub/Ubl) regulates a whole variety of cellular processes such as protein degradation, signaling, sorting, localization, activation and repression. Post-translational modification by SUMO and ubiquitin are tightly regulated in the cell by dedicated mechanisms at different levels, basically by a balance between conjugation by specific E3 ligases and deconjugation by de-ubiquitinases and/or de-SUMOylases, which cleave off SUMO/ubiquitin from targets and revert the function of the Ub/Ubl modification. In this project we will get a deeper insight into the conjugation mechanism, by the study of the SUMO E3 ligase activity of Nse2 in the context of the Smc5-Smc6 complex, and in deconjugation. All goals proposed in the project are related to the understanding of the basic molecular mechanisms behind the Ub/Ubl modification pathway, which among many functions controls the correct protein homeostasis of the cell and their malfunction is often associated to many pathologies, including tumorigenesis and other human disorders.