Michler’s hydrol blue elucidates structural differences in prion strains

Yiling Xiao, Sandra Rocha, Catherine C. Kitts, Anna Reymer, Tamás Beke-Somfai, Kendra K. Frederick, Bengt Nordén

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Yeast prions provide self-templating protein-based mechanisms of inheritance whose conformational changes lead to the acquisition of diverse new phenotypes. The best studied of these is the prion domain (NM) of Sup35, which forms an amyloid that can adopt several distinct conformations (strains) that confer distinct phenotypes when introduced into cells that do not carry the prion. Classic dyes, such as thioflavin T and Congo red, exhibit large increases in fluorescence when bound to amyloids, but these dyes are not sensitive to local structural differences that distinguish amyloid strains. Here we describe the use of Michler’s hydrol blue (MHB) to investigate fibrils formed by the weak and strong prion fibrils of Sup35NM and find that MHB differentiates between these two polymorphs. Quantum mechanical time-dependent density functional theory (TDDFT) calculations indicate that the fluorescence properties of amyloid-bound MHB can be correlated to the change of binding site polarity and that a tyrosine to phenylalanine substitution at a binding site could be detected. Through the use of site-specific mutants, we demonstrate that MHB is a site-specific environmentally sensitive probe that can provide structural details about amyloid fibrils and their polymorphs.
Original languageEnglish (US)
Pages (from-to)202001732
JournalProceedings of the National Academy of Sciences
StatePublished - Nov 10 2020
Externally publishedYes


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