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The role of the C‐terminus of human α‐synuclein: Intra‐disulfide bonds between the C‐terminus and other regions stabilize non‐fibrillar monomeric isomers
Author(s) -
Hong Dong-Pyo,
Xiong Wei,
Chang Jui-Yoa,
Jiang Chuantao
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2011.01.009
Subject(s) - random coil , chemistry , c terminus , monomer , cysteine , stereochemistry , fibril , disulfide bond , mutation , biophysics , crystallography , amino acid , biochemistry , biology , circular dichroism , gene , enzyme , organic chemistry , polymer
Substantial evidence implicates that the aggregation of α‐synuclein (αSyn) is a critical factor in the pathogenesis of Parkinson's disease. This study focuses on the role of αSyn C‐terminus. We introduced two additional cysteine residues at positions 107 and 124 (A107C and A124C) to our previous construct. Five X‐isomers of oxidative‐folded mutation of α‐synuclein with three disulfides were isolated and their secondary structures and aggregating features were analyzed. All isomers showed similar random coil structures as wild‐type α‐synuclein. However, these isomers did not form aggregates or fibrils, even with prolonged incubation, suggesting that the interactions between the C‐terminal and N‐terminal or central NAC region are important in maintaining the natively unfolded structure of αSyn and thus prevent αSyn from changing conformation, which is a critical step for fibrillation.