Predicted Fold for the Abri Amyloid Subunit: A Model for Amyloidogenesis in Familial British Dementia

ABri is a 34 residue polypeptide that forms amyloid fibrils in Familial British Dementia (FBD). A PSI-Blast search, 3 different fold recognition programs and 3D model-building indicated that it has 3 beta-strands forming an antiparallel beta-sheet and a small C-terminal alpha-helix. In order to validate the prediction, the region coding the ABri polypeptide was cloned, expressed and purified from E. Coli. Circular Dichroism (CD) spectroscopy of ABri in aqueous solution shows it to have a predominantly beta-sheet structure with a small alpha-helical component.