Characterizing the Conformational Dynamics of Human SUMO2: Insights into its Interaction with Metal Ions and SIMs

Abstract

SUMO (Small Ubiquitin‐like Modifiers) proteins are involved in a crucial post‐translational modification commonly termed as SUMOylation. In this work, we have investigated the native‐state conformational flexibility of human SUMO2 and its interaction with Cu2+ and Zn2+ ions using 15N/1H based 2D NMR spectroscopy. After SUMO1, SUMO2 is the most studied SUMO isoform in humans which shares 45% and ~80% similarity with SUMO1 in terms of sequence and structure, respectively. We show that compared to SUMO1, several amino acids in SUMO2 around α1‐helix region access energetically similar near‐native conformations. This could play a crucial role in its non‐covalent interactions with SUMO interaction motifs (SIMs). A strong binding with Cu2+ ions in the C‐terminal and resulting aggregation into timers as shown by gel‐electrophoresis studies seem to interefere in it’s non‐covalent interaction with a V/I‐x‐V/I‐V/I based SIM in Daxx protein.