Prof Steve Matthews (Imperial College Cross-Faculty NMR Centre – London)  


The small ubiquitin-like modifier (SUMO) can form polymeric chains that 
are important signals in cellular processes such as meiosis, genome 
maintenance and stress response. The SUMO-targeted ubiquitin ligase RNF4 
has a key role in the DNA damage response and in arsenic therapy for 
acute promyelocytic leukaemia. RNF4 engages with polySUMO chains of 
sumoylated substrates and catalyses their ubiquitination, which targets 
the substrate for proteasomal degradation. Structural investigation into 
the mechanisms polySUMO recognition has been hampered by the inherent 
flexibility and the production of suitable polySUMO chains. A segmental 
labelling approach combined with solution NMR spectroscopy and extensive 
biochemical characterisation reveals how RNF4 manipulates the 
conformation of the polySUMO chain thereby facilitating optimal delivery 
of the distal SUMO domain for ubiquitin transfer.

Publisert 2. mai 2014 11:40