Binding of the Molecular Chaperone αB-Crystallin to Aβ Amyloid Fibrils Inhibits Fibril Elongation
-
Altmetric Citations
Shammas, Sarah L.; Waudby, Christopher A.; Wang, Shuyu; Buell, Alexander K.; Knowles, Tuomas P.J.; Ecroyd, Heath; Welland, Mark E.; Carver, John A.; Dobson, Christopher M.; Meehan, Sarah
Description
The molecular chaperone αB-crystallin is a small heat-shock protein that is upregulated in response to a multitude of stress stimuli, and is found colocalized with Aβ 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 Aβ fibrils in vitro. We find that αB-crystallin binds to wild-type Aβ(42) fibrils with micromolar affinity, and also binds to fibrils...[Show more]
dc.contributor.author | Shammas, Sarah L. | |
---|---|---|
dc.contributor.author | Waudby, Christopher A. | |
dc.contributor.author | Wang, Shuyu | |
dc.contributor.author | Buell, Alexander K. | |
dc.contributor.author | Knowles, Tuomas P.J. | |
dc.contributor.author | Ecroyd, Heath | |
dc.contributor.author | Welland, Mark E. | |
dc.contributor.author | Carver, John A. | |
dc.contributor.author | Dobson, Christopher M. | |
dc.contributor.author | Meehan, Sarah | |
dc.date.accessioned | 2016-03-28T23:52:22Z | |
dc.date.available | 2016-03-28T23:52:22Z | |
dc.identifier.issn | 0006-3495 | |
dc.identifier.uri | http://hdl.handle.net/1885/100890 | |
dc.description.abstract | The molecular chaperone αB-crystallin is a small heat-shock protein that is upregulated in response to a multitude of stress stimuli, and is found colocalized with Aβ 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 Aβ fibrils in vitro. We find that αB-crystallin binds to wild-type Aβ(42) fibrils with micromolar affinity, and also binds to fibrils formed from the E22G Arctic mutation of Aβ(42). Immunoelectron microscopy confirms that binding occurs along the entire length and ends of the fibrils. Investigations into the effect of αB-crystallin on the seeded growth of Aβ fibrils, both in solution and on the surface of a quartz crystal microbalance biosensor, reveal that the binding of αB-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 αB-crystallin interaction with α-synuclein and insulin fibrils, the results suggest that this mechanism is a generic means of providing molecular chaperone protection against amyloid fibril formation. | |
dc.description.sponsorship | This study was supported by the Engineering and Physical Sciences Research Council, UK (S.S. and A.K.B.); Unilever and the Biotechnology and Biological Sciences Research Council (C.A.W.); the Wellcome and Leverhulme Trusts (C.M.D.); the Australian Research Council (J.A.C.); the Australian National Health and Medical Research Council; a Peter Doherty Fellowship (H.E.); a Herchel Smith Harvard Postgraduate Scholarship (S.W.); a Royal Society Dorothy Hodgkin Fellowship (S.M.); and a Bye Fellowship, Magdalene College, Cambridge (A.K.B.). | |
dc.publisher | Biophysical Society | |
dc.rights | © 2011 Biophysical Society. Open access under CC BY-NC-ND license. | |
dc.source | Biophysical Journal | |
dc.subject | amyloid beta-peptides | |
dc.subject | molecular imaging | |
dc.subject | peptide fragments | |
dc.subject | protein binding | |
dc.subject | protein structure, secondary | |
dc.subject | alpha-crystallin b chain | |
dc.subject | protein multimerization | |
dc.title | Binding of the Molecular Chaperone αB-Crystallin to Aβ Amyloid Fibrils Inhibits Fibril Elongation | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.identifier.citationvolume | 101 | |
dc.date.issued | 2011 | |
local.identifier.absfor | 030406 | |
local.identifier.ariespublication | U4217927xPUB797 | |
local.publisher.url | http://www.biophysics.org/ | |
local.type.status | Published Version | |
local.contributor.affiliation | Shammas, Sarah L., University of Cambridge, United Kingdom | |
local.contributor.affiliation | Waudby, Christopher A., University Chemical Laboratory, United Kingdom | |
local.contributor.affiliation | Wang, Shuyu, University of Cambridge, United Kingdom | |
local.contributor.affiliation | Buell, Alexander K., University of Cambridge, United Kingdom | |
local.contributor.affiliation | Knowles, Tuomas P. J., University of Cambridge, United Kingdom | |
local.contributor.affiliation | Ecroyd, Heath, University of Wollongong, Australia | |
local.contributor.affiliation | Welland, Mark E., University of Cambridge, United Kingdom | |
local.contributor.affiliation | Carver, John, College of Physical and Mathematical Sciences, CPMS Research School of Chemistry, RSC General, The Australian National University | |
local.contributor.affiliation | Dobson, Christopher M., University of Cambridge, United Kingdom | |
local.contributor.affiliation | Meehan, Sarah, University of Cambridge, United Kingdom | |
local.identifier.essn | 1542-0086 | |
local.bibliographicCitation.issue | 7 | |
local.bibliographicCitation.startpage | 1681 | |
local.bibliographicCitation.lastpage | 1689 | |
local.identifier.doi | 10.1016/j.bpj.2011.07.056 | |
local.identifier.absseo | 970103 | |
dc.date.updated | 2016-06-14T08:59:45Z | |
local.identifier.scopusID | 2-s2.0-80053379382 | |
local.identifier.thomsonID | 000295661300014 | |
dcterms.accessRights | Open Access | |
Collections | ANU Research Publications |
Download
File | Description | Size | Format | Image |
---|---|---|---|---|
01_Shammas_Binding_of_the_Molecular_2011.pdf | 902.9 kB | Adobe PDF |
Items in Open Research are protected by copyright, with all rights reserved, unless otherwise indicated.
Updated: 17 November 2022/ Responsible Officer: University Librarian/ Page Contact: Library Systems & Web Coordinator