INSTABILITY, UNFOLDING AND AGGREGATION OF HUMAN LYSOZYME VARIANTS UNDERLYING AMYLOID FIBRILLOGENESIS

Tissue deposition of soluble proteins as amyloid fibrils underlies a r ange of fatal diseases. The two naturally occurring human lysozyme var iants are both amyloidogenic, and are shown here to be unstable. They aggregate to form amyloid fibrils with transformation of the mainly he lical native fold, observed in crystal structures, to the amyloid fibr il cross-beta fold. Biophysical studies suggest that partly folded int ermediates are involved in fibrillogenesis, and this may be relevant t o amyloidosis generally.