DNA-triggered aggregation of copper, zinc superoxide dismutase in the presence of ascorbate.
The oxidative damage hypothesis proposed for the function gain of copper, zinc superoxide dismutase (SOD1) maintains that both mutant and wild-type (WT) SOD1 catalyze reactions with abnormal substrates that damage cellular components critical for viability of the affected cells. However, whether the oxidative damage of SOD1 is involved in the formation of aggregates rich in SOD1 or not remains elusive. Here, we sought to explore the oxidative aggregation of WT SOD1 exposed to environments containing both ascorbate (Asc) and DNA under neutral conditions. The results showed that the WT SOD1 protein was oxidized in the presence of Asc. The oxidation results in the higher affinity of the modified protein for DNA than that of the unmodified protein. The oxidized SOD1 was observed to be more prone to aggregation than the WT SOD1, and the addition of DNA can significantly accelerate the oxidative aggregation. Moreover, a reasonable relationship can be found between the oxidation, increased hydrophobicity, and aggregation of SOD1 in the presence of DNA. The crucial step in aggregation is neutralization of the positive charges on some SOD1 surfaces by DNA binding. This study might be crucial for understanding molecular forces driving the protein aggregation.
Yin
Jun
J
Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, and School of Chemistry, Central China Normal University, Wuhan, China.
Hu
Si
S
Jiang
Wei
W
Liu
Liang
L
Lan
Shemin
S
Song
Xuegang
X
Liu
Changlin
C
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001483:Base Sequence; D002417:Cattle; D004247:DNA / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D010084:Oxidation-Reduction; D055503:Protein Multimerization / Q000187:drug effects*; D020836:Protein Structure, Quaternary; D013482:Superoxide Dismutase / Q000737:chemistry / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
C000606290:SOD1 protein, human; D004247:DNA; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D001205:Ascorbic Acid
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