Author:
Ikeda Koki,Suzuki Shota,Shigemitsu Yoshiki,Tenno Takeshi,Goda Natsuko,Oshima Atsunori,Hiroaki Hidekazu
Abstract
AbstractThe molecular shield effect was studied for intrinsically disordered proteins (IDPs) that do not adopt compact and stable protein folds. IDPs are found among many stress-responsive gene products and cryoprotective- and drought-protective proteins. We recently reported that some fragments of human genome-derived IDPs are cryoprotective for cellular enzymes, despite a lack of relevant amino acid sequence motifs. This sequence-independent IDP function may reflect their molecular shield effect. This study examined the inhibitory activity of IDPs against fibril formation in an amyloid beta peptide (Aβ(1–42)) model system. Four of five human genome-derived IDPs (size range 20 to 44 amino acids) showed concentration-dependent inhibition of amyloid formation (IC50 range between 60 and 130 μM against 20 μM Aβ(1–42)). The IC50 value was two orders of magnitude lower than that of polyethylene-glycol and dextran, used as neutral hydrophilic polymer controls. Nuclear magnetic resonance with 15 N-labeled Aβ(1–42) revealed no relevant molecular interactions between Aβ(1–42) and IDPs. The inhibitory activities were abolished by adding external amyloid-formation seeds. Therefore, IDPs seemed to act only at the amyloid nucleation phase but not at the elongation phase. These results suggest that IDPs (0.1 mM or less) have a molecular shield effect that prevents aggregation of susceptible molecules.
Funder
Japan Agency for Medical Research and Development
Japan Society for the Promotion of Science
Publisher
Springer Science and Business Media LLC
Cited by
11 articles.
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