Theoretical Investigations of the Effects

of the Cellular Environmenton Protein Folding

Joan-Emma Shea

UCSB Chemistry

Proteins play a critical role in most cellular processes but in order to perform their function, they must rapidly fold from a linear sequence of amino acids to a stable three-dimensional structure. Proteins do not always fold properly and a number of diseases, such as Alzheimer’s disease and Type II diabetes, are associated with this failure. In the case of Alzheimer’s disease, incorrectly folded Amyloid-beta (A b ) proteins self-assemble into a variety of neurotoxic aggregate species, ranging from small soluble oligomers to amyloid fibrils. The cell has evolved a number of defense mechanisms against protein misfolding, including the use of chaperonin molecules that recognize misfolded proteins and help guide them to their correct native state. In this talk, I will discuss some of our recent theoretical investigations of protein aggregation and chaperonin-mediated protein folding.