title: Using multiple structural proteomics approaches for the characterization of prion proteins.
abstract: Structural proteomics approaches are valuable tools, particularly in cases where the exact mechanisms of protein conformational changes or the structures of proteins and protein complexes cannot be elucidated by traditional structural biology techniques like X-ray crystallography or NMR methods. Each structural proteomics method can provide a different set of data, all of which can be used as structural constraints for modeling the protein. We have applied a combination of limited proteolysis, surface modification, chemical crosslinking, and hydrogen/deuterium exchange for the characterization of structural differences in prion proteins in native monomeric and in the aggregated β-oligomeric states. Data from these multiple proteomics approaches are in remarkable agreement in pointing to the rearrangement of the beta sheet 1-helix1-beta sheet 2-helix 2 (β1-H1-β2-H2) region as a major conformational change between the native and oligomeric prion protein forms. This data is also consistent with the β1-H1-β2 loop moving away from the H2-H3 core during the prion protein conversion. This is an example of how complementary data from multiple structural proteomics approaches can provide novel insights into the three-dimensional structures of proteins and protein complexes. This article is part of a Special Issue entitled: From protein structures to clinical applications.
authors.affiliation: University of Victoria-Genome British Columbia Proteomics Centre, University of Victoria, #3101-4464 Markham Street, Vancouver Island Technology Park, Victoria, British Columbia, Canada V8Z 7X8.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Serpa
authors.forename: Aileen P
authors.initials: AP
authors.lastname: Patterson
authors.forename: Jingxi
authors.initials: J
authors.lastname: Pan
authors.forename: Jun
authors.initials: J
authors.lastname: Han
authors.forename: David S
authors.initials: DS
authors.lastname: Wishart
authors.forename: Evgeniy V
authors.initials: EV
authors.lastname: Petrotchenko
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Borchers
mesh_terms: D000818:Animals; D006224:Cricetinae; D008647:Mesocricetus; D008958:Models, Molecular; D011328:Prions / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D059748:Proteolysis; D040901:Proteomics
chemical_list: D011328:Prions