Structure of the cross-β spine of amyloid-like fibrils

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-β spine. It is a double β-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. Probing prions Alzheimer's, prion diseases and other neurodegenerative disorders are associated with insoluble protein fibres called amyloid fibrils. Gathering structural information about these has proved difficult, but three groups now report success with contrasting approaches to the problem. The cover shows the atomic structure of the ‘spine’ of an amyloid-like fibril formed by the yeast prion protein Sup35. To obtain this structure, Nelson et al . performed X-ray crystallography on amyloid microcrystals. Krishnan and Lindquist used a raft of techniques to study folding of the amyloid core. And Ritter et al . determined the infectious conformation of HET-s prion of a filamentous fungus. Christopher Dobson ponders on what this flood of structural data says about prion and amyloid formation in sickness and in health.