Ubiquitination

Regulated degradation of proteins is an important process of controlling gene expression and has pivotal roles in the control of various cellular processes. Proteins targeted for degradation are conjugated with chains of multiple ubiquitin molecules and degraded by the 26S proteasome. The step of ubiquitin conjugation (also known as ubiquitylation), involves a series of well-defined reactions catalyzed by enzymes classified into three types: ubiquitin -activating enzyme (E1), -conjugating enzyme (E2) and –ligase (E3). Our interests involve the enzymes found in the process of Endoplasmic Reticulum Associated Degradation, or ERAD. In collaboration with Allan Weissman’s laboratory, we have been examining several E2:E3 pairs of proteins. We have studied both the structures (using NMR and X-ray crystallography) and the binding interactions within the active complexes of these processes. An example of our multi-disciplinary approach is found in Mol. Cell 34(6) 674-685 (2009).