Imaging amyloid beta peptide oligomeric particles in solution.
While all protein misfolding diseases are characterized by fibrous amyloid deposits, the favorable free energy and strongly cooperative nature of the self-assembly have complicated the development of therapeutic strategies aimed at preventing their formation. As structural models for the amyloid fibrils approach atomic resolution, increasing evidence suggests that early folding intermediates, rather than the final structure, are more strongly associated with the loss of neuronal function. For that reason we now demonstrate the use of cryo-etch high-resolution scanning electron microscopy (cryo-HRSEM) for the direct observation of pathway intermediates in amyloid assembly. A congener of the Abeta peptide of Alzheimer's disease, Abeta(13-21), samples a variety of time-dependent self-assembles in a manner similar to those seen for larger proteins. A morphological description of these intermediates is the first step towards their structural characterization and the definition of their role in both amyloid assembly and neurotoxicity.
Center for the Analysis of SupraMolecular Self-assemblies, Integrated Microscopy and Microanalytical Facility, Department of Chemistry, Emory University, 1521 Dickey Drive, Atlanta, GA 30322, USA.
Jijun
J
Dong
Robert P
RP
Apkarian
David G
DG
Lynn
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001704:Biopolymers / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D010446:Peptide Fragments / Q000737:chemistry*; D012996:Solutions
D016229:Amyloid beta-Peptides; D001704:Biopolymers; D010446:Peptide Fragments; D012996:Solutions