Characterization of Cu2+ and Zn2+ binding sites in SUMO1 and its impact on protein stability.

摘要: Abstract Metal ions like Cu2+ and Zn2+ have been shown to impact protein misfolding pathways in neurodegenerative proteinopathies Alzheimer's Parkinson's. Also, due their strong interaction with Ubiquitin, they interfere degradation of misfolded proteins by impairing the ubiquitin-proteasome system (UPS). In this work, we studied these metal a small Ubiquitin post-translation modifier SUMO1, which is known work co-operatively regulate UPS system. Between Zn2+, former binds more strongly SUMO1 as determined using fluorescence spectroscopy. aggregates, forming trimer higher oligomers presence were characterized gel electrophoresis, Bradford assay, transmission electron microscopy. Chemical shift analysis 15N/1H based NMR spectroscopy revealed that retains its structural fold trimeric state. induced paramagnetic quenching chemical perturbation 15N-1H cross-peaks used identify respective binding sites SUMO1. Binding so obtained further validated molecular dynamics studies. Our findings provide insights into SUMO1-Cu2+/Zn2+ interaction, on aggregation might affect ability modify functions target proteins.