Folding and Self-assembly of the Domains of beta B2-Crystallin from Rat Eye Lens

beta B2-Crystallin from vertebrate eye lens forms domain-swapped dimers, with subunits consisting of two all- beta domains connected by an eight-residue extended linker peptide. Topologically, the two domains show great similarity; however, they differ widely in their stability. As shown by urea-induced equilibrium unfolding experiments, the isolated monomeric C-terminal domain is more stable than complete beta B2. In contrast, the N-terminal domain exhibits marginal stability only in its dimeric state; upon subunit dissociation, at low protein concentration, unfolding takes place. The folding and association of intact beta B2 follows a sequential uni-bimolecular mechanism according to N sub(2)[rlhar2]2 I[rlhar2]2U, whereas the isolated domains may be quantitatively described by the two-state model (N[lrhar2]U).