Probing fibril dissolution of the repeat domain of a functional amyloid, Pmel17, on the microscopic and residue level

Ryan P. McGlinchey, James M. Gruschus, Attila Nagy, Jennifer C. Lee

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15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)10567-10569
Number of pages3
JournalBiochemistry
Volume50
Issue number49
DOIs
Publication statusPublished - Dec 13 2011

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ASJC Scopus subject areas

  • Biochemistry

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