BIOT 62 |
| Proteins must fold into just the right shape to do their jobs. When proteins misfold, they are usually degraded by vigilant cellular quality-control mechanisms. However, some misfolded proteins persist in their altered shapes. In humans, the consequences can be deadly, leading to devastating illnesses such as Alzheimer's and Parkinson's diseases. In the special case of prion proteins, altered forms can template their change in shape to other proteins of the same type, leading to transmissible spongiform encephalopathies like “mad cow.” In yeast cells, however, prions are not toxic, but can actually provide helpful new phenotypes. For example, one yeast prion is formed from an inactive, misfolded translation-termination factor. The altered form is passed from mother cells to daughters, acting as a “seed” to perpetuate the prion state. This results in changes in gene expression and many new phenotypes. Remarkably, in collaboration with Eric Kandel and Kausik Si, we have also found that a protein that plays an important role in synaptic plasticity behaves as a prion in yeast, and postulate that the self-perpetuating folding of its prion domain can act as a molecular memory. In both cases the prion is an amyloid, difficult to study by conventional methods. We are devising a variety of new tools to determine how prion proteins fold and template their own conformations. |
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Perlman Lecture
4:30 PM-5:30 PM, Sunday, August 19, 2007 BCEC -- 107 A/B, Oral
Division of Biochemical Technology |