| Understanding protein structures is important to understanding how proteins function, and how these functions might be enhanced or inhibited. A better understanding of protein structures and folding may also lead to the development of medical tools for amyloid diseases, which arise from protein misfolding. Interestingly, the majority of amyloid proteins appear to be composed of parallel beta-sheets. Of the common protein secondary structures, parallel beta-sheets are the least characterized, in large part because they are difficult to isolate. Minimal folding units of parallel beta-sheets -- i.e., short peptides that can fold into these structures in the absence of other structural contexts -- can be used to garner important information about sheets, but are challenging design and synthesize. Here we report the first experimental model of a three-stranded parallel beta sheet (Chapter 2), and use this model system to study the effect of the number of strands on parallel beta sheet stability.;The relationship between size and stability for the parallel beta sheet is important to characterize from a basic science perspective, and is also of interest because amyloid structures appear to grow via a propagation of parallel beta sheet structure. In Chapter 3 we demonstrate how bioinformatics studies can inform the de novo design of minimal models of protein secondary and tertiary structures. We design a water-soluble, minimal model of amyloid-like structure, and use it to explore hydrophobic interactions involved in amyloid formation. Model systems like ours may contribute to understandings of protein structure, stability, and interactions. |
