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

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, Sarah Meehan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

139 Citations (Scopus)


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 Alzheimers 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.

Original languageEnglish
Pages (from-to)1681-1689
Number of pages9
JournalBiophysical Journal
Issue number7
Publication statusPublished - 5 Oct 2011
Externally publishedYes


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