Prion Structure

Yeast Prion Biology

Proteins that can acquire self-perpetuating changes in structure with associated changes in function (prions) constitute a newly discovered mechanism of heredity: changes in phenotype can be passed from generation to generation through heritable changes in protein conformation with no underlying changes in nucleic acids. We have provided cell biological, genetic, and biochemical evidence that this mechanism controls the inheritance of a regulator of the fidelity of protein synthesis, known as [PSI+]. We have also discovered a remarkable similarity in the types of mutations that control the inheritance of [PSI+] and those that govern the heritable forms of TSE diseases. Most recently, we have been focusing on determining how many other proteins are capable of producing heritable switches in conformation and function and in determining if this mechanism can serve as a new, general method for the genetic manipulation of phenotype.

Selected Recent Publications on Prions

Reviews:

Shorter J and Lindquist SL, 2005. Prions as adaptive conduits of memory and inheritance. Nat Rev Genet. 6: 435-50.[PDF 824KB]

Serio TR and Lindquist SL, 1999. [PSI+]: An epigenetic modulator of translation termination efficiency. Annual Review of Cell and Developmental Biology 15: 661-703.

Lindquist S, 1997. Mad cows meet psi-chotic yeast: The expansion of the prion hypothesis. Cell 89: 495-98. [PDF 48KB]

Research Papers:

Tyedmers J, Madariaga ML, Lindquist S, 2008. Prion Switching in Response to Environmental Stress. PLoS Biol 6(11): e294. [PDF 488 KB]

Misfolded proteins accelerate yeast evolution (WIBR press release)
Prion switching in response to environmental stress (PLoS Biology news release)

Shorter J, Lindquist S, 2008. Hsp104, Hsp70 and Hsp40 interplay regulates formation, growth and elimination of Sup35 prions. EMBO J 27(20): 2712-24. [PDF 2.1 MB]

Halfmann R, Lindquist S, 2008. Screening for Amyloid Aggregation by Semi-Denaturing Detergent-Agarose Gel Electrophoresis. J Visualized Experiments 17: 7/16/2008, doi: 10.3791/838. [JoVE video link]

This article was covered in MIT's The Tech: "Meet JoVE: The YouTube Of Scientific Journals" By Zeina Siam

Douglas PM, Treusch S, Ren H-Y, Halfmann R, Duennwald ML, Lindquist S, Cyr DM, 2008. Chaperone-dependent amyloid assembly protects cells from prion toxicity. Proc Natl Acad Sci USA 105(20): 7206–11. [PDF 1 MB]

Alberti S, Gitler AD and Lindqsuit S, 2007. A suite of Gateway™ cloning vectors for high-throughput genetic analysis in Saccharomyces cerevisiae. Yeast 24(10):913-919. [PDF 972 KB]

Si K, Lindquist S, Kandel ER, 2003. A Neuronal Isoform of the Aplysia CPEB Has Prion-Like Properties. Cell 115:879-91. [PDF 636KB]

Sondheimer N and Lindquist S, 2000. Rnq1, an epigenetic modifier of protein function in yeast. Molecular Cell 5: 1-20.[PDF 348KB]

Li L and Lindquist S, 2000. Creating a protein-based element of inheritance. Science 287: 661-664.[PDFLink]

Glover JR, Kowal AS, Schirmer EC, Patino MM, Liu J-J, and Lindquist S, 1997. Self-seeded fibers formed by Sup35, the protein determinant of [PSI+], a heritable prion-like factor of Saccharomyces cerevisiae. Cell 89:811-819. [PDF 272 KB]

Patino MM, Liu J-J, Glover JR and Lindquist S, 1996. Support for the prion hypothesis for inheritance of a phenotypic trait in yeast. Science 273:622-626. [PDF1.88 MB]