The binding of thioflavin-T to amyloid fibrils: localisation and implications

Krebs, MRH; Bromley, EHC; Donald, AM

Abstract

Amyloid fibrils are a polymeric form of protein, involving a continuous P-sheet with the strands perpendicular to the long axis of the fibril. Although typically implicated in diseases such as Alzheimer's disease and the transmissible spongiform encephalopathies, non disease-associated protein can also be converted into amyloid fibrils. Traditionally, amyloid fibrils are identified via the use of specific dyes such as Congo red and thioflavin-T, although their specificity is ill understood. Recently, solutions of bovine insulin and bovine beta-lactoglobulin have been found to form spherulites, micron-sized spherical structures containing radially arranged amyloid fibrils. When studied by confocal microscopy using polarised laser light and thioflavin-T, a consistent pattern of emission, rather than a uniform disc, was observed. This suggests the dye binds in a specific, regular fashion to amyloid fibrils. Confocal microscopy studies of thioflavin-T aligned in stretched poly-vinyl alcohol films showed that the dye dipole excitation axis lies parallel to the long molecular axis. Therefore, thioflavin-T binds to amyloid fibrils such that their long axes are parallel. We propose binding occurs in 'channels' that run along the length of the beta-sheet. Steric interactions between dye molecules and side chains indicate why thioflavin-T fluoresces more intensely when bound to amyloid fibrils and can explain why this interaction with amyloid fibrils is specific, but with varying efficiency. (C) 2004 Elsevier Inc. All rights reserved.

Citation

Krebs, M., Bromley, E., & Donald, A. (2005). The binding of thioflavin-T to amyloid fibrils: localisation and implications. Journal of Structural Biology, 149(1), 30-37. https://doi.org/10.1016/j.jsb.2004.08.002

• Journal Article Type: Article
• Publication Date: 2005
• Journal: Journal of Structural Biology
• Print ISSN: 1047-8477
• Publisher: Elsevier
• Volume: 149
• Issue: 1
• Pages: 30-37
• DOI: https://doi.org/10.1016/j.jsb.2004.08.002
• Public URL: https://durham-repository.worktribe.com/output/1522349