Amyloid and prion structures

Abstract

Protein aggregation diseases, including amyloid and prion diseases, are accompanied by the deposition of elongated, unbranched protein fibrils having similar tinctural and diffraction properties. Our research group has determined atomic structures for some 45 different segments of fibril‐forming proteins which in isolation from the rest of the protein form fibrils and microcrystals, and find that the atomic structures display common characteristics. The segments are selected by a computer algorithm from the sequences of proteins known to form amyloid‐like fibrils, and are then synthesized and crystallized by conventional methods. Because amyloid crystals are invariably smaller than ordinary protein crystals by a factor of 10,000, X‐ray diffraction data from them must be recorded on a microcrystallography synchrotron beam line. The atomic structures may be termed steric zippers, a newly recognized class of protein structures. Steric zippers are formed from the intermeshing of two beta sheets. In each sheet, extended protein strands hydrogen bond to each other up and down the fibril, forming either a parallel or antiparallel sheet. Then two sheets intermesh in one of eight possible ways, to form the steric zipper