Conformational Dynamics and metal-ion interactions in human small Ubiquitin-like modifier (SUMO2)

SUMO (Small Ubiquitin-like Modifiers) proteins are involved in a crucial post-translational modification commonly termed as SUMOylation. Currently little is known about localisation and accumulation of SUMO2 conjugates in response to proteasome inhibitors. In this work, we have investigated a strong binding of Cu2+ ions in the C-terminal region of SUMO2 resulting in its aggregation and seems to interefere in its non-covalent interaction with a V/I-X-V/I-V/I based SIM. In Ubiquitin-proteasome system, SUMO2 controls many targets in regulation of all aspects of metabolism. The conformational flexibility of SUMO2 could play a crucial role, therefore we have also characterized native-state flexibility of human SUMO2. We show that compared to SUMO1, several amino acids in SUMO2 around 1-helix region access energetically similar near-native conformations. This could play a fundamental role in its non-covalent interactions with SUMO interaction motifs (SIMs).