title: Templating molecular arrays in amyloid's cross-beta grooves.
abstract: Amyloid fibers, independent of primary amino acid sequence, share a common cross-beta structure and bind the histochemical dye Congo Red (CR). Despite extensive use of CR in amyloid diagnostics, remarkably little is known about the specific and characteristic binding interactions. Fibril insolubility, morphological inhomogeneity, and multiple possible ligand binding sites all conspire to limit characterization. Here, we have exploited the structure of cross-beta nanotubes, which limit the number of potential binding sites, to directly interrogate cross-beta laminate grooves. CR bound to cross-beta nanotubes displays the hallmark apple-green interference color, a broad red-shifted low energy transition, and a K(d) of 1.9 +/- 0.5 microM. Oriented electron diffraction and linear dichroism defines the orientation of CR as parallel to the amyloid long axis and colinear with laminate grooves. The broad red-shifted UV signature of CR bound to amyloid can be explained by semiempirical quantum calculations that support the existence of a precise network of J- and H-CR aggregates, illuminating the ability of the amyloid to organize molecules into extended arrays that underlie the remarkable diagnostic potential of CR.
authors: Center for Fundamental and Applied Molecular Evolution, and Department of Chemistry and Biology, Emory University, Atlanta, Georgia 30322, USA.
authors: W Seth
authors: WS
authors: Childers
authors: Anil K
authors: AK
authors: Mehta
authors: Kun
authors: K
authors: Lu
authors: David G
authors: DG
authors: Lynn
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D001665:Binding Sites; D003224:Congo Red / Q000737:chemistry*; D015336:Molecular Probe Techniques; D043942:Nanotubes / Q000737:chemistry*
chemical_list: D000682:Amyloid; D003224:Congo Red