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Binding Modes of Thioflavin T on the Surface of Amyloid Fibrils Studied by NMR
Author(s) -
Ivancic Valerie A.,
Ekanayake Oshini,
Lazo Noel D.
Publication year - 2016
Publication title -
chemphyschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.016
H-Index - 140
eISSN - 1439-7641
pISSN - 1439-4235
DOI - 10.1002/cphc.201600246
Subject(s) - thioflavin , chemistry , fibril , monomer , crystallography , lysozyme , nuclear magnetic resonance spectroscopy , intermolecular force , molecule , biophysics , stereochemistry , biochemistry , polymer , organic chemistry , medicine , disease , pathology , biology , alzheimer's disease
The mechanism for the interaction of thioflavin T (ThT) with amyloid fibrils at the molecular level is not known. Here, we used 1 H NMR spectroscopy to determine the binding mode of ThT on the surface of fibrils from lysozyme and insulin. Relayed rotating‐frame Overhauser enhancements in ThT were observed, indicating that the orientation of ThT is orthogonal to the fibril surface. Importantly, the assembly state of ThT on both surfaces is different. On the surface of insulin fibrils, ThT is oligomeric, as indicated by rapid 1 H spin‐lattice relaxation rate in the rotating frame ( R 1 ρ ), presumably due to intermolecular dipole–dipole interactions between ThT molecules. In contrast, ThT on the surface of lysozyme fibrils is a monomer, as indicated by slower 1 H R 1 ρ . These results shed new light into the mechanism for the enhancement of ThT fluorescence and may lead to more efficient detectors of amyloid assemblies, which have escaped detection by ThT in monomer form.