The Involvement of His50 during Protein Disulfide Isomerase Binding Is Essential for Inhibiting α-Syn Fibril Formation.

An increased level of protein disulfide isomerase (PDI) is a protective response to various neurodegenerative disorders, including Parkinson's disease. Interaction of PDI with α-synuclein (α-Syn) has been shown to inhibit its aggregation. Here, we report the residue-specific mapping of binding of PDI to α-Syn. We demonstrate that α-Syn N-terminal residues ...
V3-S9 and L38-V40 bind more strongly to PDI than residues V49-V52 do, as do C-terminal residues E123-M127 and D135-E137. In addition, we show that residue H50 is key in preventing aggregation. These findings improve our understanding of PDI-protected aggregation of wild-type α-Syn and its H50Q familial mutant.
Mesh Terms:
Amino Acid Substitution, Amyloid, Animals, Histidine, Humans, Mutation, Missense, Parkinson Disease, Protein Disulfide-Isomerases, alpha-Synuclein
Biochemistry
Date: Dec. 17, 2015
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