Introduction
Our group studies the molecular mechanisms underlying cell signaling and in particular protein ubiquitylation using NMR spectroscopy, X-ray crystallography and biochemical methods. Many proteins localize in the cell to specific compartments and function only for a limited amount of time. To remove mislocalized or no longer required proteins ubiquitin, a ~10 kD protein, is attached to these proteins. The ubiquitylation reaction involves three enzymes whose exact catalytic mechanisms are unknown. Mutations in ubiquitylation enzymes give rise to severe cellular dysfunctions that cause numerous human diseases including cancer. We seek to understand how ubiquitylation enzymes function on an atomic level, how their activities are controlled and how ubiquitylation regulates cellular behavior.