title: Probing fibril dissolution of the repeat domain of a functional amyloid, Pmel17, on the microscopic and residue level.
abstract: Pmel17 is a human amyloid involved in melanin synthesis. A fragment of Pmel17, the repeat domain (RPT) rich in glutamic acids, forms amyloid only at mildly acidic pH. Unlike pathological amyloids, these fibrils dissolve at neutral pH, supporting a reversible aggregation-disaggregation process. Here, we study RPT dissolution using atomic force microscopy and solution-state nuclear magnetic resonance spectroscopy. Our results reveal asymmetric fibril disassembly proceeding in the absence of intermediates. We suggest that fibril unfolding involves multiple deprotonation events resulting in electrostatic charge repulsion and filament dissolution.
authors.affiliation: Laboratory of Molecular Biophysics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, United States.
authors.forename: Ryan P
authors.initials: RP
authors.lastname: McGlinchey
authors.forename: James M
authors.initials: JM
authors.lastname: Gruschus
authors.forename: Attila
authors.initials: A
authors.lastname: Nagy
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Lee
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D018625:Microscopy, Atomic Force; D017434:Protein Structure, Tertiary; D058951:gp100 Melanoma Antigen / Q000737:chemistry*
chemical_list: D000682:Amyloid; D058951:gp100 Melanoma Antigen
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