Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/68189
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Type: Journal article
Title: Binding of the molecular chaperone alpha B-crystallin to A beta amyloid fibrils Inhibits fibril elongation
Author: Shammas, S.
Waudby, C.
Wang, S.
Buell, A.
Knowles, T.
Ecroyd, H.
Welland, M.
Carver, J.
Dobson, C.
Meehan, S.
Citation: Biophysical Journal, 2011; 101(7):1681-1689
Publisher: Biophysical Society
Issue Date: 2011
ISSN: 0006-3495
1542-0086
Statement of
Responsibility: 
Sarah L. Shammas, Christopher A. Waudby, Shuyu Wang, Alexander K. Buell, Tuomas P. J. Knowles, Heath Ecroyd, Mark E. Welland, John A. Carver, Christopher M. Dobson, and Sarah Meehan
Abstract: The molecular chaperone aB-crystallin is a small heat-shock protein that is upregulated in response to a multitude of stress stimuli, and is found colocalized with Ab amyloid fibrils in the extracellular plaques that are characteristic of Alzheimer’s disease. We investigated whether this archetypical small heat-shock protein has the ability to interact with Ab fibrils in vitro. We find that aB-crystallin binds to wild-type Ab42 fibrils with micromolar affinity, and also binds to fibrils formed from the E22G Arctic mutation of Ab42. Immunoelectron microscopy confirms that binding occurs along the entire length and ends of the fibrils. Investigations into the effect of aB-crystallin on the seeded growth of Ab fibrils, both in solution and on the surface of a quartz crystal microbalance biosensor, reveal that the binding of aB-crystallin to seed fibrils strongly inhibits their elongation. Because the lag phase in sigmoidal fibril assembly kinetics is dominated by elongation and fragmentation rates, the chaperone mechanism identified here represents a highly effective means to inhibit fibril proliferation. Together with previous observations of aB-crystallin interaction with a-synuclein and insulin fibrils, the results suggest that this mechanism is a generic means of providing molecular chaperone protection against amyloid fibril formation.
Keywords: Peptide Fragments; alpha-Crystallin B Chain; Protein Structure, Secondary; Protein Binding; Protein Multimerization; Molecular Imaging; Amyloid beta-Peptides
Rights: Copyright 2011 by the Biophysical Society
RMID: 0020113089
DOI: 10.1016/j.bpj.2011.07.056
Description (link): http://www.cell.com/biophysj
Appears in Collections:Chemistry publications

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