Probing Fibril Dissolution of the Repeat Domain of a Functional Amyloid, Pmel17, on the Microscopic and Residue Level

Overview

Journal Biochemistry

Specialty Biochemistry

Date 2011 Nov 19

PMID 22092386

Citations 14

Authors

Ryan P McGlinchey

James M Gruschus

Attila Nagy

Jennifer C Lee

Affiliations

Soon will be listed here.

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.

Citing Articles

Observation of pH-Dependent Residual Structure in the Pmel17 Repeat Domain and the Implication for Its Amyloid Formation.

Morris D, Nyenhuis D, Dean D, Strub M, Tjandra N Biochemistry. 2023; 62(22):3222-3233.

PMID: 37917797 PMC: 11822675. DOI: 10.1021/acs.biochem.3c00445.

Monitoring Kinetics of pH-Dependent Aggregation and Disaggregation of the Pmel17 Repeat Domain.

Dean D, Lee J Methods Mol Biol. 2022; 2551:79-93.

PMID: 36310198 DOI: 10.1007/978-1-0716-2597-2_7.

Purification and characterization of an amyloidogenic repeat domain from the functional amyloid Pmel17.

Dean D, Lee J Protein Expr Purif. 2021; 187:105944.

PMID: 34293440 PMC: 8403166. DOI: 10.1016/j.pep.2021.105944.

Linking Parkinson's Disease and Melanoma: Interplay Between α-Synuclein and Pmel17 Amyloid Formation.

Dean D, Lee J Mov Disord. 2021; 36(7):1489-1498.

PMID: 34021920 PMC: 8316358. DOI: 10.1002/mds.28655.

Modulating functional amyloid formation via alternative splicing of the premelanosomal protein PMEL17.

Dean D, Lee J J Biol Chem. 2020; 295(21):7544-7553.

PMID: 32277052 PMC: 7247297. DOI: 10.1074/jbc.RA120.013012.

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