Key Facts

Abstract:
Ubiquitination is achieved through a co-ordinated enzymatic cascade of E1, E2, and E3 ligases. E1 ubiquitin activating enzymes are the initiators of ubiquitination. In most metazoans two E1 ubiquitin activating enzymes exist: UBA1 and the non-canonical E1, UBA6. Recently, we and others have discovered that the E2 and regulator of cell death and development, BIRC6, functions exclusively with UBA6. Both UBA6 and BIRC6 are essential for normal development and brain specific UBA6 knockout mice display neurological disorders. Despite their functional importance, how E2 ubiquitin-conjugating enzymes function exclusively with UBA6 is not understood. Through trapping stable complexes of E2s receiving ubiquitin from UBA6 we are uncovering the molecular determinants of E2 specificity. Our work will provide the fundamental molecular understanding crucial for investigating the non-canonical ubiquitination pathway in cellular processes.
Bio:
I completed my PhD at the University of Leicester under the supervision of Professor Peter Moody learning the dark arts of protein crystallography. I then moved to the University of Liverpool where I was a postdoc with Dr Igor Barsukov and Professor Lu-Yun Lian using NMR and crystallography to study the cell adhesion protein Talin. A collaboration with Professors Mike Clague and Sylvie Urbé in Liverpool ignited my interest in the small protein, ubiquitin. This led me to join the lab of Dr David Komander at the MRC Laboratory of Molecular Biology, Cambridge, where I became an Investigator Scientist. In 2018 I established my independent group in the Department of Biochemistry with an MRC Career Development Award.