ANS binding reveals common features of cytotoxic amyloid species

Authors

Benedetta Bolognesi, University of Cambridge
Janet R. Kumita, University of Cambridge
Teresa P. Barros, University of Cambridge
Elin K. Esbjorner, University of Cambridge
Leila M. Luheshi, University of Cambridge
Damian C. Crowther, University of Cambridge
Mark R. Wilson, University of WollongongFollow
Christopher M. Dobson, University of CambridgeFollow
Giorgio Favrin, University of Cambridge
Justin J. Yerbury, University of WollongongFollow

RIS ID

33829

Publication Details

Bolognesi, B., Kumita, J. R., Barros, T. P., Esbjorner, E. K., Luheshi, L. M., Crowther, D. C., Wilson, M. R., Dobson, C. M., Favrin, G. & Yerbury, J. J. (2010). ANS binding reveals common features of cytotoxic amyloid species. ACS Chemical Biology, 5 (8), 735-740.

Abstract

Oligomeric assemblies formed from a variety of disease-associated peptides and proteins have been strongly associated with toxicity in many neurodegenerative conditions, such as Alzheimer's disease. The precise nature of the toxic agents, however, remains still to be established. We show that prefibrillar aggregates of E22G (arctic) variant of the A beta(1-42) peptide bind strongly to 1-anilinonaphthalene 8-sulfonate and that changes in this property correlate significantly with changes in its cytotoxicity. Moreover, we show that this phenomenon is common to other amyloid systems, such as wild-type A beta(1-42), the 159T variant of human lysozyme and an SH3 domain. These findings are consistent with a model in which the exposure of hydrophobic surfaces as a result of the aggregation of misfolded species is a crucial and common feature of these pathogenic species.