Binding of the molecular chaperone alpha B-crystallin to A beta amyloid fibrils Inhibits fibril elongation
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 archetypica...
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ftunivadelaidedl:oai:digital.library.adelaide.edu.au:2440/68189 2023-12-17T10:26:26+01:00 Binding of the molecular chaperone alpha B-crystallin to A beta amyloid fibrils Inhibits fibril elongation Shammas, S. Waudby, C. Wang, S. Buell, A. Knowles, T. Ecroyd, H. Welland, M. Carver, J. Dobson, C. Meehan, S. 2011 http://hdl.handle.net/2440/68189 https://doi.org/10.1016/j.bpj.2011.07.056 en eng Biophysical Society ARC Biophysical Journal, 2011; 101(7):1681-1689 0006-3495 1542-0086 http://hdl.handle.net/2440/68189 doi:10.1016/j.bpj.2011.07.056 Copyright 2011 by the Biophysical Society http://dx.doi.org/10.1016/j.bpj.2011.07.056 Peptide Fragments alpha-Crystallin B Chain Protein Structure Secondary Protein Binding Protein Multimerization Molecular Imaging Amyloid beta-Peptides Journal article 2011 ftunivadelaidedl https://doi.org/10.1016/j.bpj.2011.07.056 2023-11-20T23:18:32Z 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. 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 http://www.cell.com/biophysj Article in Journal/Newspaper Arctic The University of Adelaide: Digital Library Arctic Knowles ENVELOPE(-60.883,-60.883,-71.800,-71.800) Biophysical Journal 101 7 1681 1689 |
institution |
Open Polar |
collection |
The University of Adelaide: Digital Library |
op_collection_id |
ftunivadelaidedl |
language |
English |
topic |
Peptide Fragments alpha-Crystallin B Chain Protein Structure Secondary Protein Binding Protein Multimerization Molecular Imaging Amyloid beta-Peptides |
spellingShingle |
Peptide Fragments alpha-Crystallin B Chain Protein Structure Secondary Protein Binding Protein Multimerization Molecular Imaging Amyloid beta-Peptides Shammas, S. Waudby, C. Wang, S. Buell, A. Knowles, T. Ecroyd, H. Welland, M. Carver, J. Dobson, C. Meehan, S. Binding of the molecular chaperone alpha B-crystallin to A beta amyloid fibrils Inhibits fibril elongation |
topic_facet |
Peptide Fragments alpha-Crystallin B Chain Protein Structure Secondary Protein Binding Protein Multimerization Molecular Imaging Amyloid beta-Peptides |
description |
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. 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 http://www.cell.com/biophysj |
format |
Article in Journal/Newspaper |
author |
Shammas, S. Waudby, C. Wang, S. Buell, A. Knowles, T. Ecroyd, H. Welland, M. Carver, J. Dobson, C. Meehan, S. |
author_facet |
Shammas, S. Waudby, C. Wang, S. Buell, A. Knowles, T. Ecroyd, H. Welland, M. Carver, J. Dobson, C. Meehan, S. |
author_sort |
Shammas, S. |
title |
Binding of the molecular chaperone alpha B-crystallin to A beta amyloid fibrils Inhibits fibril elongation |
title_short |
Binding of the molecular chaperone alpha B-crystallin to A beta amyloid fibrils Inhibits fibril elongation |
title_full |
Binding of the molecular chaperone alpha B-crystallin to A beta amyloid fibrils Inhibits fibril elongation |
title_fullStr |
Binding of the molecular chaperone alpha B-crystallin to A beta amyloid fibrils Inhibits fibril elongation |
title_full_unstemmed |
Binding of the molecular chaperone alpha B-crystallin to A beta amyloid fibrils Inhibits fibril elongation |
title_sort |
binding of the molecular chaperone alpha b-crystallin to a beta amyloid fibrils inhibits fibril elongation |
publisher |
Biophysical Society |
publishDate |
2011 |
url |
http://hdl.handle.net/2440/68189 https://doi.org/10.1016/j.bpj.2011.07.056 |
long_lat |
ENVELOPE(-60.883,-60.883,-71.800,-71.800) |
geographic |
Arctic Knowles |
geographic_facet |
Arctic Knowles |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
http://dx.doi.org/10.1016/j.bpj.2011.07.056 |
op_relation |
ARC Biophysical Journal, 2011; 101(7):1681-1689 0006-3495 1542-0086 http://hdl.handle.net/2440/68189 doi:10.1016/j.bpj.2011.07.056 |
op_rights |
Copyright 2011 by the Biophysical Society |
op_doi |
https://doi.org/10.1016/j.bpj.2011.07.056 |
container_title |
Biophysical Journal |
container_volume |
101 |
container_issue |
7 |
container_start_page |
1681 |
op_container_end_page |
1689 |
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1785578147379412992 |