Templating molecular arrays in amyloid's cross-beta grooves

Area of Science:

• Biochemistry
• Structural Biology
• Biophysics

Background:

• Amyloid fibers share a common cross-beta structure and bind Congo Red (CR), a dye crucial for diagnostics.
• The precise binding interactions of CR with amyloid structures remain poorly understood due to fibril insolubility and heterogeneity.

Purpose of the Study:

• To elucidate the specific binding interactions between Congo Red and amyloid structures.
• To characterize the orientation and aggregation state of CR when bound to amyloid.

Main Methods:

• Utilized cross-beta nanotubes to limit potential CR binding sites.
• Employed Congo Red binding assays, electron diffraction, and linear dichroism.
• Performed semiempirical quantum calculations to model CR aggregation.

Main Results:

• CR binding to cross-beta nanotubes exhibited the characteristic apple-green interference color and a K(d) of 1.9 +/- 0.5 microM.
• Electron diffraction and linear dichroism determined CR orientation parallel to the amyloid long axis and laminate grooves.
• Quantum calculations supported the formation of J- and H-CR aggregates.

Conclusions:

• Amyloid structures organize CR into precise J- and H-aggregate networks.
• This molecular organization explains the diagnostic utility of Congo Red for amyloid detection.