PROBING THE INFLUENCE OF ARGININE METHYLATION ON THE MODULATION OF BIOMOLECULAR

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Our original goals were to investigate the influence of arginine methylation on biomolecular interactions. This took a sideline as our investigations into Alzheimer's and prion disease were more fruitful. Therefore in our year three extension we altered our goals to probe the neurotoxic consequences of copper coordination to the prion protein and amyloid-beta peptides. Our goals are to: 1) determine the Cu(I) and Cu(II) coordination geometries within different isomorphs of the prion protein and amyloid-beta peptide as coordination geometry directly influence metal center reactivity, 2) probe how mutations to these proteins influence the coordination geometry of copper, 3) examine the ability of these copper-metalloproteins/metallopeptides to support catalytic reactive oxygen species production and 4) examine how the interaction between the copper, the prion-protein and amyloid-beta influence neurotxicity as such a link has been suggested in the biochemical literature.