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

• Published in: Chembiochem : a European journal of chemical biology Vol. 25; no. 11; pp. e202400045 - n/a
• Main Authors: Kaur, Anupreet, Singh, Harpreet, Kumar, Dinesh, Gahlay, Gagandeep Kaur, Mithu, Venus Singh
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 03.06.2024
• Subjects: Amino acids; Conformational dynamics; Copper; Daxx protein; Electrophoresis; Magnetic resonance spectroscopy; Metal ions; Metal-protein interaction; NMR spectroscopy; Protein NMR; Protein structure; Proteins; SUMO protein; SUMO2; Ubiquitin; Zinc; SUMO2 NMR spectroscopy Protein NMR Metal-protein interaction Conformational dynamics
• ISSN: 1439-4227; 1439-7633; 1439-7633
• DOI: 10.1002/cbic.202400045

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. 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. SUMO2 exhibits conformational flexibility in the α1‐helix region, potentially influencing its interactions with SUMO interaction motifs (SIMs) on target molecules, crucial for SUMOylation. The SUMO2‐SIM interaction is hindered in the presence of Cu2+ ions, possibly due to Cu2+‐induced trimerization and subsequent aggregation of SUMO2.