Investigating the essential roles of Ubiquitin-like molecules and the Ubiquitin Proteasome System

Research Project 3.
Cellular roles of atypical Ub chains.

Objectives

The main objective is to characterize the cellular roles of atypical Ub chains linked via K6, K11, K27, K29 or K33. We start with purified Ub chains of particular linkages and identify DUBs that act specifically on atypical linkages. This enables structural and functional studies of linkage-specific enzymes. Our key strengths lie in structural analysis, and we use X-ray crystallography, NMR, small-angle X-ray scattering (SAXS) and single-molecule approaches to study complexes of Ub chains with proteins. Our methodologies to assemble Ub chain of atypical linkages enzymatically and chemically have made these linkage types available for the first time and have opened new areas of Ub research.

Partner

MRC