"NMR WRESTLING WITH SUMO CHAINS"
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.