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

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 Cu 2+ and Zn 2+ ions using 15 N‐ 1 H 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. In this manuscript, we demonstrate that compared to SUMO1, several amino acids around the α 1 ‐helix region of SUMO2 access energetically similar near‐native conformations. These conformations could play a crucial role in SUMO2’s non‐covalent interactions with SUMO interaction motifs (SIMs) on other proteins. The C‐terminal of SUMO2 was found to bind strongly with Cu 2+ ions resulting in a trimeric structure as observed by gel electrophoresis. This interaction seems to interfere in its non‐covalent interaction with a V/I‐x‐V/I‐V/I based SIM in Daxx protein.