Editor's Summary
8 September 2005
Prions: form and infectivity
The prospects of limiting the spread of transmissible spongiform encephalopathies such as Creutzfeldt−Jakob disease depend in part on identifying the most infectious forms of the prions that carry the diseases. A study of modified scrapie prions shows that clusters of 14 to 28 prion proteins are the most infectious and that clusters of less than six molecules have virtually no infectivity. That could have implications for the treatment of diseases such as Alzheimer's and Parkinson's, characterized by deposition of prion-related amyloid fibrils. It's possible that efforts to alleviate symptoms by destabilizing these large protein aggregates might make things worse by producing smaller, more infective particles. Two other papers in this issue tackle fundamental aspects of the biology of prions and amyloid fibrils. The conversion of the yeast protein Sup35 to its prion form does not need to happen during the synthesis of Sup35 — mature and fully functional molecules can readily join a prion seed. This remodelling of the mature protein is accompanied by the immediate loss of its activity. And a study of a 'designed' amyloid fibril made from ribonuclease A reveals that amyloid containing native-like molecules can retain enzyme activity. This involves a domain swap with the neighbouring protein, and supports the 'zipper-spine model' for 
-amyloid structures.
News and Views: Structural biology: Fibres hinge on swapped domains
When proteins assemble themselves into fibres, there can be grave pathological consequences. Designing an otherwise soluble protein to make fibres provides a general mechanism for the construction process.
Andrew D. Miranker
doi: 10.1038/437197a
Letter: The most infectious prion protein particles
Jay R. Silveira, Gregory J. Raymond, Andrew G. Hughson, Richard E. Race, Valerie L. Sim, Stanley F. Hayes and Byron Caughey
doi: 10.1038/nature03989
First paragraph | Full Text | PDF (442K) | Supplementary information
Letter: Prion protein remodelling confers an immediate phenotypic switch
Prasanna Satpute-Krishnan and Tricia R. Serio
doi: 10.1038/nature03981
First paragraph | Full Text | PDF (343K) | Supplementary information
Letter: Amyloid-like fibrils of ribonuclease A with three-dimensional domain-swapped and native-like structure
Shilpa Sambashivan, Yanshun Liu, Michael R. Sawaya, Mari Gingery and David Eisenberg
doi: 10.1038/nature03916
First paragraph | Full Text | PDF (357K) | Supplementary information
