Scientists have grappled for years with one of the central tenets of the protein-only hypothesis, namely, that a single prion protein, when unaltered by genetic mutation, can give rise to different strains of prions with varying infectivity and other properties. The two research groups established that the strains could be accounted for by different misfolded conformations of the same protein. The researchers say this finding could contribute to better understanding of the functioning of disease-causing prions in animals and humans.
Both groups published their findings in the March 18, 2004, issue of the journal Nature. Howard Hughes Medical Institute investigator Jonathan Weissman at the University of California, San Francisco led one group. The other effort was led by Chi-Yen King at Florida State University.
Both groups worked with yeast prions, which are similar to the mammalian prions known to cause fatal brain-destroying human diseases such as Creutzfeldt-Jakob disease and kuru, and the animal diseases bovine spongiform encephalopathy ("mad cow disease") and scrapie.
Scientists theorize that both yeast and mammalian prions transmit their characteristics via protein-protein interactions, in which an abnormally folded prion influences its normal counterpart to assume an irregular conformation.
In mammalian prion infections, abnormal, insoluble shapes trigger protein clumping that can kill brain cells. In yeast cells, the insoluble prion protein is not deadly; it merely alters a cell's metabolism.
Contact: Jim Keeley
Howard Hughes Medical Institute