NR AURS
AU Schwarzinger,S.; Horn,A.H.C.; Ziegler,J.; Sticht,H.
TI Rare subdomain motions in prion protein can initiate aggregation
QU TSE-Forum, 6. Kongress - Nationale TSE-Forschungsplattform, Greifswald 26.6.-28.6.2006, Poster: Struktur und molekulare Mechanismen MOL-16
PT Konferenz-Poster
AB The prion protein is thought to induce transmissible spongiform encephalopathies, such as Creutzfeldt-Jakob disease (CJD) in man or bovine spongiform encephalopathy (BSE) in cattle, by changing its conformation from the cellular form, PrPc, into the infectious Scrapie-form, PrPsc. Little is known about the structural and dynamical features of this conformational change. We here present a novel concept involving rare large scale motions between the subdomains ß1-alpha1-ß2 and alpha2-alpha3 in the carboxy-terminal, globular part of PrPc. The interface between these two subdomains carries a significant number of destabilizing, pathogenic mutations known to be associated with prion diseases. Based on computational simulations as well as experimental results we propose that such a large scale motion subsequently destabilizes large parts of the cellular conformer PrPc thus rendering it susceptible to structural rearrangements, including aggregation of now partially unfolded parts of the PrP sequence. We hypothesize that such large scale motions occur as a rare event even under equilibrium conditions and that the interaction of such partially destabilized PrPc-conformers, which we name PrPc*, contributes to the formation of infectious oligomeric species of the prion protein.
AD Stephan Schwarzinger, Jan Ziegler, Lehrstuhl Biopolymere, Universität Bayreuth, Universitätsstrasse 30, 95440 Bayreuth; Anselm H. C. Horn, Heinrich Sticht, Abteilung Bioinformatik, Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander Universität, Fahrstrasse 17, 91054 Erlangen
SP englisch
PO Deutschland
EA pdf-Datei, Übersicht, oben, unten
OR Tagungsband