NR AQHP
AU Baxa,U.; Ross,P.D.; Wickner,R.B.; Steven,A.C.
TI The N-terminal prion domain of Ure2p converts from an unfolded to a thermally resistant conformation upon filament formation
QU Journal of Molecular Biology 2004 May 28; 339(2): 259-64
PT journal article
AB According to the "amyloid backbone" model of Ure2p prionogenesis, the N-terminal domain of Ure2p polymerizes to form an amyloid filament backbone surrounded by the C-terminal domains. The latter domains retain their native glutathione-S-transferase (GST)-like fold but are sterically inactivated from their regulatory role in nitrogen catabolism. We have tested this model by differential scanning calorimetry of soluble and filamentous Ure2p and of soluble C-terminal domains, combined with electron microscopy. As predicted, the C-terminal domains respond to thermal perturbation identically in all three states, exhibiting a single endotherm at 76 degrees C. In contrast, no thermal signal was associated with the N-terminal domains: in the soluble state of Ure2p, because they are unfolded; in the filamentous state, because their robust amyloid conformation resists heating to 100 degrees C.
MH Calorimetry, Differential Scanning; Heat; Microscopy, Electron, Scanning; Prions/*chemistry/ultrastructure; Protein Conformation; Protein Denaturation; Saccharomyces cerevisiae Proteins/*chemistry/ultrastructure
AD Laboratory of Structural Biology, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
SP englisch
PO England