Guo-Ping Zhou
Gordon Life Science Institute, Boston, USA
Title: The Study of the Misfolding Mechanism of the Prion Protein by Incorporating the Wenxiang Diagrams into NMR Spectroscopy
Biography
Biography: Guo-Ping Zhou
Abstract
The conversion of a normal native-helix-rich prion protein (PrPc) to an abnormal polymeric ß-sheet-rich configuration (PrPsc) is a misfolding process. PrPsc is a disease associated fibril-forming isoform such as transmissible spongiform encephalopathies (TSEs) or prion diseases, a deadly disease occurred in both humans and many vertebrate animals. Our NMR studies have indicated that the misfolding process from PrPc to PrPsc is related to the unwinding and stability of the original α-helix structures in PrPc protein. Recently, we have also built up the wenxiang diagrams of all three helices (H1-H2-H3) of PrPc and observed that most hydrophobic residues of the all three helices (H1-H2-H3) in PrPc are distinctly distributed in one-half of the wenxiang diagram of each helix, and most hydrophilic residues are distributed in the other half of the wenxiang diagrams. Similarly, most residues formed salt bridges or ionic pairs in an-helical structure are close to each other in a wenxiang diagram plane. According to these features, the helix-helix interactions, stability of alpha-helical structure, as well as possible interactions between the helix and residues outside the helix (the residues in loops) can be quickly inferred and further verified incorporating NMR spectroscopy. Our results explain why H1 is the most stable helix, and H2 is the most unstable helix during the formation process of prion disease. Thus, the incorporation of the wenxiang diagrams into NMR may provide more insight on the molecular mechanisms of the protein misfolding diseases.