Amphoterin includes a sequence motif which is homologous to the Alzheimer's beta-amyloid peptide (A beta), forms amyloid fibrils in vitro, and binds avidly to A beta

Many of the proteins associated with amyloidoses have been found to share s tructural and sequence similarities, which are believed to be responsible f or their capability to form amyloid fibrils. Interestingly, some proteins s eem to be able to form amyloid-like fibrils although they are not associate d with amyloidoses. This indicates that the ability to form amyloid fibrils may be a general property of a greater number of proteins not associated w ith these diseases. In the present work, we have searched for amyloidogenic consensus sequences in two current protein/peptide databases and show that many proteins share structures which can be predicted to form amyloid. One of these potentially amyloidogenic proteins is amphoterin (also known as H MG-1), involved in neuronal development and a ligand for the receptor for a dvanced glycation end products (RAGE). It contains an amyloidogenic peptide fragment which is highly homologous to the Alzheimer's amyloid beta -pepti de. If enzymatically released from the native protein, it forms amyloid-lik e fibrils which are visible in electron microscopy, exhibit apple green bir efringence under polarized light after Congo red staining, and increases th ioflavin T fluorescence. This fragment also shows high affinity to A beta a s a free peptide or while part of the native protein. Our results support t he hypothesis that the potential to form amyloid is a common characteristic of a number of proteins, independent of their relation to amyloidoses, and that this potential can be predicted based on the physicochemical properti es of these proteins.