1. Howard Hughes Medical Institute, UCLA-DOE Institute for Genomics and Proteomics, Box 951570, UCLA, Los Angeles, California 90095-1570, USA
2. Centre for Crystallographic Studies, Department of Chemistry, University of Copenhagen, Universitetsparken 5, DK-2100 KBH, Denmark
3. European Synchrotron Radiation Facility, B.P. 220, F-38043 Grenoble Cedex, France

Correspondence to: David Eisenberg¹ Correspondence and requests for materials should be addressed to D.E. (Email: david@mbi.ucla.edu).
The structures of GNNQQNY and NNQQNY have been deposited in the Protein Data Bank with accession codes 1yjp and 1yjo, respectively.

Abstract

Numerous soluble proteins convert to insoluble amyloid-like fibrils that have common properties. Amyloid fibrils are associated with fatal diseases such as Alzheimer's, and amyloid-like fibrils can be formed in vitro. For the yeast protein Sup35, conversion to amyloid-like fibrils is associated with a transmissible infection akin to that caused by mammalian prions. A seven-residue peptide segment from Sup35 forms amyloid-like fibrils and closely related microcrystals, from which we have determined the atomic structure of the cross- spine. It is a double -sheet, with each sheet formed from parallel segments stacked in register. Side chains protruding from the two sheets form a dry, tightly self-complementing steric zipper, bonding the sheets. Within each sheet, every segment is bound to its two neighbouring segments through stacks of both backbone and side-chain hydrogen bonds. The structure illuminates the stability of amyloid fibrils, their self-seeding characteristic and their tendency to form polymorphic structures.

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