Studying the possible link between mammalian prion shape and strains has proven very difficult, but three different prions have also been identified in yeast, a powerful model in research aimed at understanding human genetic mechanisms. The UCSF study applies the versatile organism to studies of proteins and prion infectivity.
"The existence of different prion strains has been one of the most fascinating and puzzling features of prion biology," said Jonathan Weissman, PhD, a Howard Hughes Medical Institute investigator and professor of cellular and molecular pharmacology at UCSF. Weissman is senior author of the paper.
"With these studies we now have compelling evidence that the ability of proteins to misfold into multiple amyloid forms constitutes the physical foundation of the strain phenomenon. The challenge now is to understand what distinguishes the different structures in the different prion strains, and how these different structures change a prion's properties -- including how dangerous they are."
In their laboratory at UCSF's Mission Bay campus, Weissman and his colleagues introduced misfolded forms of a yeast prion protein into normal (prion-free) yeast. The yeast cells were grown in conditions that cause normal yeast organisms to form small, red colonies, while yeast infected with prions, termed [PSI+], form colonies of different colors. They found that introduction of the misfolded prion form yielded yeast "infected" with the [PSI+] prion.
Like prions that cause mammalian disease, the prions in yeast naturally exist in several different forms or strains. To explore the link between prion strains and the conformation of the misfolded proteins in the
Contact: Wallace Ravven
University of California - San Francisco