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

Abstract

AbstractSUMO (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. In this manuscript, we demonstrate that compared to SUMO1, several amino acids around the α1‐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 Cu2+ 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.