Physics Special Colloquium, March 10, 2005

Structural Investigations of Amyloid Fibrils by Solid State NMR

Aneta T. Petkova

Laboratory of Chemical Physics, NIDDK, National Institutes of Health

Amyloid fibrils are the major component of plaques that accumulate in different organs as a result of various conformational diseases. The detailed molecular structures of amyloid fibrils have been largely unknown due to their inherent insolubility and non-crystallinity. However, they are perfectly amenable to advanced high-resolution solid state NMR methods that provide site-specific, molecular-level structural information concerning order, secondary structure, supramolecular organization of the beta sheets (parallel or antiparallel), and tertiary constraints. The experiments that led to the development of the first molecular model of Alzheimer's beta-amyloid fibrils (Petkova et al. (2002), PNAS 99: 16742) will be described, and the molecular interactions that stabilize the amyloid fibrils will be discussed. Recent results detailing self-propagating variations in molecular structure that underlie the amyloid polymorphism commonly observed in electron microscope images (Petkova et al. (2005), Science 307: 262), and our current structural model for the Alzheimer's beta-amyloid fibrils will be shown. Implications of the experimental data for our understanding of fibril formation mechanisms, strains of prion diseases, and pathogenicity of amyloid fibrils will be discussed.

10:30 a.m., Room 4138 PRB (Physics Research Building)

Refreshments served at 10:00 a.m.