A DNA G-quadruplex converts SOD1 into fibrillar aggregates  

作　　者：Wenqian Liu Yulin Xu Xue Li Yan Meng Huiling Wang Chunrong Liu Changlin Liu Li Wang 

机构地区：[1]Key Laboratory of Pesticide&Chemical Biology,Ministry of Education,and School of Chemistry,Central China Normal University,Wuhan 430079,China [2]Wuhan No.1 Huiquan Middle School,Wuhan 430022,China

出　　处：《Chinese Chemical Letters》2021年第7期2322-2326,共5页中国化学快报（英文版）

基　　金：financially supported by the National Natural Science Foundation of China(Nos.21771073,22077046,21001047,21072074);the Fundamental Research Funds for the Central Universities(No.CCNU19TS052)。

摘　　要：Nucleic acids with G4 elements play a role in the formation of aggregates involved in intracellular phase transitions.Our previous studies suggest that different forms of DNA could act as an accelerating template in Cu/Zn superoxide dismutase(SOD1)aggregation.Here,we examined the regulation of fo rmation and cytotoxicity of the SOD1 aggregates by single-stranded 12-merdeoxynucleotide oligomers(dN)_(12)(N=A,T,G,C;ssDNAs)under acidic conditions.The ssDNAs can be divided into two groups based on their roles in SOD1 binding,exposure of hydrophobic clusters in SOD1,accelerated formation,morphology and cytotoxicity of SOD1 aggregates.G-quadruplexes convert SOD1 into fibrillar aggregates as a template,a fact which was observed for the first time in the nucleic acid regulation of protein aggregation.Moreover,the fibrillar or fibril-like SOD1 species with a G-quadruplex provided by(dG)_(12)were less toxic than the amorphous species with(dN)_(12)(N=A,T).This study not only indicates that both morphology and cytotoxicity of protein aggregates can be regulated by the protein-bound DNAs,but also help us understand roles of nucleic aid G-quadruplexes in the formation of aggregates and membrane less organelles involved in intracellular phase transitions.

关 键 词：SOD1 Deoxynucleotide oligomers(dN)_(12) G-QUADRUPLEXES Fibrillar aggregates 

分 类 号：Q523[生物学—生物化学]