Prions cause neurodegenerative diseases in humans and animals. The infectious prions are largely composed of a host encoded glycoprotein denoted PrP-Sc. Limited digestion of PrP-Sc by proteinase K yields an N- terminally truncated polypeptide corresponding primarily to residues 90- 231, which remains infectious when injected into normal healthy animal. We are studying the structure of recombinant Syrian Hamster Prion Protein rPrP(90-231) using multi-dimensional NMR. We use the NMR spectral analysis and database management program (SPARKY) to assign the backbone and sidechain 1H, 13C and 15N resonances of the protein. The assignment for over 3000 NOEs and the management of the data for about 1000 proton resonances are also made using SPARKY. In the structure refinement process, we constantly use molecular graphics (MidasPlus) to check the results of our calculations, and display the NMR constraints with the program noeshow. The interactive process of examining the structure and adding in restraints is heavily dependent on graphics since we have such a great deal of spectral overlap. Finally we use the molecular graphics capabilities of MidasPlus to produce figures for publications and presentations.
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