Project Details
Projekt
Conformational switching during the production of branched polyubiquitin chains (A13*)
Subject Area
Biochemistry
Term
from 2021 to 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 201302640
Post-translational modification by ubiquitin chains is a major form of eukaryotic protein regulation. Although much is known about E1-E2-E3 trienzyme cascades linking ubiquitin to target proteins, the dynamic structural mechanisms underlying formation of specific ubiquitin chains – and particularly roles of E4 enzymes – are poorly understood. In this project, we will investigate the mechanisms of conformational switching during generation and recognition of specific "branched" ubiquitin chains (wherein lysines 29 and 48 of an individual molecule of ubiquitin are both isopeptide bonded to additional ubiquitin molecules) by E1-E2-E3-E4 tetraenzyme cascades. Biochemistry, chemistry, X-ray crystallography, and cryo EM will be used to elucidate the dynamic conformational cycles by which three individual ubiquitins are site-specifically adjoined by E2-E3 and E2-E4 enzyme pairs. Furthermore, principles of polyubiquitylation will be determined.
DFG Programme
Collaborative Research Centres
Applicant Institution
Technische Universität München (TUM)
Project Head
Professorin Dr. Brenda Schulman
