US researchers suggest that a single protein gives different prion properties.
US researchers suggest that a single protein gives different prion properties.
Prions have always courted controversy. At first, many scientists didn’t believe that these abnormal forms of protein even existed. Then, after their existence had been proved, some scientists still doubted whether the prions alone could be responsible for infectious diseases such as scrapie, bovine spongiform encephalopathy (BSE) and Creutzfeldt-Jakob disease, the human version of BSE.
Now, in articles recently published in Nature, two teams of US researchers have independently demonstrated that prions can replicate within cells, without the help of any genetic material, and that different prion strains are the result of the same protein folding in different ways. ’[The researchers] provide the most dramatic demonstration to date of the validity of the protein-only hypothesis’, says Mick Tuite of the University of Kent in a comment on the study.
One of the main challenges for the protein-only hypothesis was explaining how different prion strains, which have contrasting properties, can be derived from the same protein without its underlying amino acid sequence being genetically altered. ’People speculated that the nucleic acid was there, but you just couldn’t find it,’ says Chih-Yen King from Florida State Univerity, Tallahassee, US.
King investigated three strains of yeast prion. The strains are all derived from the protein Sup35, which is involved in protein synthesis in yeast cells. He and co-author Ruben Diaz-Avalos created purified versions of the three prion strains and then introduced single strains into uninfected yeast cells. They discovered that the prions would infect the cell and replicate within it in a strain-specific manner 1.
Researchers at the University of California, San Francisco also investigated Sup35. They showed that the same protein fragment would adopt different conformations with changing temperatures, and that infecting yeast cells with these different conformations led to different prion strains 2.
Both studies suggest that the properties of individual prion strains result from a single protein misfolding in different ways, and that this aberrant folding can be transferred to normal versions of the protein.
Jon Evans
References
1. C-Y King, R Diaz-Avalos, Nature, 2004, 428, 319
2. P Chien, J S Weissman, Nature, 2004, 428, 223
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