Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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End-to-end Structural Restriction of α-Synuclein and Its Influence on Amyloid Fibril Formation

  • Hong, Chul-Suk (School of Chemical and Biological Engineering, Institute of Chemical Processes, College of Engineering, Seoul National University) ;
  • Park, Jae Hyung (School of Chemical and Biological Engineering, Institute of Chemical Processes, College of Engineering, Seoul National University) ;
  • Choe, Young-Jun (School of Chemical and Biological Engineering, Institute of Chemical Processes, College of Engineering, Seoul National University) ;
  • Paik, Seung R. (School of Chemical and Biological Engineering, Institute of Chemical Processes, College of Engineering, Seoul National University)
  • Received : 2014.07.21
  • Accepted : 2014.08.19
  • Published : 2014.12.20
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Abstract

Relationship between molecular freedom of amyloidogenic protein and its self-assembly into amyloid fibrils has been evaluated with ${\alpha}$-synuclein, an intrinsically unfolded protein related to Parkinson's disease, by restricting its structural plasticity through an end-to-end disulfide bond formation between two newly introduced cysteine residues on the N- and C-termini. Although the resulting circular form of ${\alpha}$-synuclein exhibited an impaired fibrillation propensity, the restriction did not completely block the protein's interactive core since co-incubation with wild-type ${\alpha}$-synuclein dramatically facilitated the fibrillation by producing distinctive forms of amyloid fibrils. The suppressed fibrillation propensity was instantly restored as the structural restriction was unleashed with ${\beta}$-mercaptoethanol. Conformational flexibility of the accreting amyloidogenic protein to pre-existing seeds has been demonstrated to be critical for fibrillar extension process by exerting structural adjustment to a complementary structure for the assembly.

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