The GdmCl-induced equilibrium unfolding and dissociation of the dimeric yeast prion protein Ure2, and its prion domain deletion mutants Delta15-42Ure2 and 90Ure2, was studied by small angle X-ray scattering (SAXS) using synchrotron radiation and by chemical cross-linking with dithiobis(succinimidyl propionate) (DTSP). The native state is globular and predominantly dimeric prior to the onset of unfolding. R-g values of 32 and 45 A were obtained for the native and 5 M GdmCl denatured states of Delta15-42Ure2, respectively; the corresponding values for 90Ure2 were 2-3 Angstrom lower. SAXS suggests residual structure in the 4 M GdmCl denatured state and chemical cross-linking detects persistence of dimeric structure under these conditions. Hexamers consisting of globular subunits could be detected by SAXS at high protein concentration under partially denaturing conditions. The increased tendency of partially folded states to form small oligomers points to a mechanism for prion formation. (C) 2003 Elsevier Inc. All rights reserved.