title: Suppression of amyloid fibrils using the GroEL apical domain.
abstract: In E. coli cells, rescue of non-native proteins and promotion of native state structure is assisted by the chaperonin GroEL. An important key to this activity lies in the structure of the apical domain of GroEL (GroEL-AD) (residue 191-376), which recognizes and binds non-native protein molecules through hydrophobic interactions. In this study, we investigated the effects of GroEL-AD on the aggregation of various client proteins (α-Synuclein, Aβ42, and GroES) that lead to the formation of distinct protein fibrils in vitro. We found that GroEL-AD effectively inhibited the fibril formation of these three proteins when added at concentrations above a critical threshold; the specific ratio differed for each client protein, reflecting the relative affinities. The effect of GroEL-AD in all three cases was to decrease the concentration of aggregate-forming unfolded client protein or its early intermediates in solution, thereby preventing aggregation and fibrillation. Binding affinity assays revealed some differences in the binding mechanisms of GroEL-AD toward each client. Our findings suggest a possible applicability of this minimal functioning derivative of the chaperonins (the "minichaperones") as protein fibrillation modulators and detectors.
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering Tottori University, Tottori 680-8552, Japan.
authors.forename: Bimlesh
authors.initials: B
authors.lastname: Ojha
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering Tottori University, Tottori 680-8552, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Fukui
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering Tottori University, Tottori 680-8552, Japan.|Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Tottori 680-8552, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Hongo
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering Tottori University, Tottori 680-8552, Japan.|Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Tottori 680-8552, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Mizobata
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering Tottori University, Tottori 680-8552, Japan.|Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Tottori 680-8552, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawata
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D018835:Chaperonin 10 / Q000737:chemistry / Q000378:metabolism; D018834:Chaperonin 60 / Q000737:chemistry* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D066263:Protein Aggregation, Pathological / Q000378:metabolism / Q000517:prevention & control; D011485:Protein Binding; D011487:Protein Conformation; D000072417:Protein Domains; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D018835:Chaperonin 10; D018834:Chaperonin 60; D029968:Escherichia coli Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D051844:alpha-Synuclein; C075222:amyloid beta-protein (1-42)