Characterisation of amyloid fibril formation by small heat-shock chaperone proteins human alpha A-, alpha beta- and R120G alpha B-Crystallins
Meehan, S., Knowles, T.P., Baldwin, A.J., Smith, J.F., Squires, A.M., Clements, P., Treweek, T.M., Ecroyd, H., Tartaglia, G.G., Vendruscolo, M., MacPhee, C.E., Dobson, C.M. and Carver, J.A. (2007) Characterisation of amyloid fibril formation by small heat-shock chaperone proteins human alpha A-, alpha beta- and R120G alpha B-Crystallins. Journal of Molecular Biology, 372 (2). pp. 470-484. ISSN 0022-2836
Full text not archived in this repository.
To link to this article DOI: 10.1016/j.jmb.2007.06.060
alpha B-Crystallin is a ubiquitous small heat-shock protein (sHsp) renowned for its chaperone ability to prevent target protein aggregation. It is stress-inducible and its up-regulation is associated with a number of disorders, including those linked to the deposition of misfolded proteins, such as Alzheimer's and Parkinson's diseases. We have characterised the formation of amyloid fibrils by human alpha B-crystallin in detail, and also that of alpha A-crystallin and the disease-related mutant R120G (alpha B-crystallin. We find that the last 12 amino acid residues of the C-terminal region of alpha B-crystallin are predicted from their physico-chemical properties to have a very low propensity to aggregate. H-1 NMR spectroscopy reveals that this hydrophilic C-terminal region is flexible both in its solution state and in amyloid fibrils, where it protrudes from the fibrillar core. We demonstrate, in addition, that the equilibrium between different protofilament assemblies can be manipulated and controlled in vitro to select for particular alpha B-crystallin amyloid morphologies. Overall, this study suggests that there could be a fine balance in vivo between the native functional sHsp state and the formation of amyloid fibrils. (C) 2007 Elsevier Ltd. All rights reserved.