CUED Publications database

Binding of the molecular chaperone αB-crystallin to Aβ amyloid fibrils inhibits fibril elongation.

Shammas, SL and Waudby, CA and Wang, S and Buell, AK and Knowles, TPJ and Ecroyd, H and Welland, ME and Carver, JA and Dobson, CM and Meehan, S (2011) Binding of the molecular chaperone αB-crystallin to Aβ amyloid fibrils inhibits fibril elongation. Biophys J, 101. pp. 1681-1689.

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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.

Item Type: Article
Uncontrolled Keywords: Amyloid beta-Peptides Molecular Imaging Peptide Fragments Protein Binding Protein Multimerization Protein Structure, Secondary alpha-Crystallin B Chain
Divisions: Div B > Solid State Electronics and Nanoscale Science
Depositing User: Cron Job
Date Deposited: 17 Jul 2017 18:58
Last Modified: 22 Jun 2018 20:35