GO DARTMOUTH!!! Cofactor Molecules Induce Structural Transformation during Infectious Prion Formation. ncbi.nlm.nih.gov/pubmed/24120764 Structure. 2013 Oct 8. pii: S0969-2126(13)00347-X. doi: 10.1016/j.str.2013.08.025. [Epub ahead of print] Miller MB, Wang DW, Wang F, Noble GP, Ma J, Woods VL Jr, Li S, Supattapone S. Source Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. Abstract The spread of misfolded proteins may occur in many neurodegenerative diseases. Mammalian prions are currently the only misfolded proteins in which high specific biological infectivity can be produced in vitro. Using a system that generates infectious prions de novo from purified recombinant PrP and conversion cofactors palmitoyl-oleoyl-phosphatidylglycerol (POPG) and RNA, we examined by deuterium exchange mass spectrometry (DXMS) the stepwise protein conformational changes that occur during prion formation. We found that initial incubation with POPG causes major structural changes in PrP involving all three α helices and one β strand, with subsequent addition of RNA rendering the N terminus highly exposed. Final conversion into the infectious PrPSc form was accompanied by globally decreased solvent exposure, with persistence of the major cofactor-induced conformational features. Thus, we report that cofactor molecules appear to induce major structural rearrangements during prion formation, initiating a dynamic sequence of conformational changes resulting in biologically active prions. Copyright © 2013 Elsevier Ltd. All rights reserved.
Posted on: Tue, 15 Oct 2013 21:13:41 +0000
Trending Topics
Recently Viewed Topics
© 2015