Activation, regulation, and biological roles of E3 ubiquitin ligases

Activation, regulation, and biological roles of E3 ubiquitin ligases

Project details

Stability, activity, location and interactions of proteins inside a human cell are tightly regulated by post-translational modifications. Arguably the most complex of the post-translational modifications is ubiquitination, which involves the conjugation of the small protein ubiquitin to target proteins.

Ubiquitination is ultimately catalysed by the E3 ubiquitin ligases. Dr Lechtenberg has provided key insights into the catalytic mechanism and regulation of the family of RING-between-RING (RBR) E3 ubiquitin ligases (Lechtenberg, Nature 2016 529(7587):546). RBR ligases control critical functions in the cell, including innate immunity, autophagy, and transcription, and are linked to many diseases, for example, cancer and autoimmunity.

In your project, you will investigate the molecular mechanisms and biological roles of medically relevant but understudied RBR ligases using structural biology, biochemical, biophysical, and cell biological techniques.

 

About our research group

My lab will start in the newly established Ubiquitin Signalling division in early 2019. The lab will utilise a multi-disciplinary approach to investigate novel and understudied E3 ubiquitin ligases, with a particular interest in the family of RING-between-RING (RBR) E3 ligases.

We aim to comprehensively study these E3 ligases from the molecular details of their catalytic mechanism and their regulation all the way to their functions in their larger signalling pathways in the human cell by combining structural biology, biochemical, biophysical, and cell biological methods. Our ultimate goal is to link fundamental biological insights with a translational approach to develop novel drug candidates and treatment options in various diseases, with an initial focus on cancer and autoimmune diseases.

 

Protein structure
Structure of the HOIP RBR E3 ubiquitin ligase (green) in complex with
an E2-ubiquitin conjugate (orange-cyan) and a regulatory ubiquitin molecule (blue).

 

Researchers:

Dr Bernhard Lechtenberg profile photo
Dr
Bernhard
Lechtenberg

Project Type: