Prion Infectivity Explained in Yeast Prions
Scientists at Whitehead Institute have discovered important regions in yeast prions that explain their ability, and potentially the ability of prions in general, to self-propagate or "infect". By analyzing yeast prions, researchers were able to identify specific recognition elements that control the switch from non-infectious to infectious conformations. Their findings are published in the May 9 online issue of the journal Nature.
"These findings provide a new framework for us to begin exploring properties of prion biology that, up until now, have proven difficult to investigate," said Whitehead Member and MIT Professor of Biology Susan Lindquist, who is also the senior author on the paper.
Prions, or proteinaceous infectious particles, are proteins that are most well known for their roles in mad cow and Creutzfeldt-Jakob disease. The protein that prions originate from is normally found in the body in a non-infectious and non-harmful form. Infectious prions have a different structure than non-infectious prions, and have the ability to convert the prion protein into an infectious form. These misformed proteins can then clump together and form fibers called amyloids, leading to disease.
However, it should be noted that not all prions are harmful, and recent research has revealed that some prions are involved in learning and memory.
In this study, Peter Tessier, a postdoctoral scientist working with Lindquist, used peptide or protein arrays to observe protein folding and amyloid formation. In the protein array, a glass slide was spotted with many different protein fragments from baker's yeast. Tessier then added yeast prion protein to the array, and looked for amyloid formation on the array.
Tessier identified a small cluster of peptides that recruited the prion proteins and caused them to misfold into an amyloid structure. He performed the same experiment with a different fungus with similar results. The researchers called the region of the protein responsible for interacting with the peptide a recognition element.
Tessier and Lindquist also believe that prions likely contain more than one recognition element, which helps to explain why some prions can jump between species while others cannot.
By identifying the recognition element in yeast prions with protein arrays, the researchers hope to perform similar experiments with mammalian samples to identify recognition regions in mammalian prions. Tessier and Lindquist believe finding these regions may provide new insights into mad cow and Creutzfeldt-Jakob disease, as well as other illnesses, such as Alzheimer's disease, that may be associated with amyloid formation.
Written by Charles Tran