Protein fibrils termed amyloid-like are associated with numerous degenerative diseases as well as some normal cellular functions. Specific short segments of amyloid-forming proteins have been shown to form fibrils themselves. However, it has not been shown in general that these segments are capable of driving a protein from its native structure into the amyloid state. We applied the 3D profile method to identify fibril-forming segments within the amyloid-forming human proteins tau, alpha-synuclein, PrP prion and amyloid-beta. Ten segments, six to eight residues in length, were chosen and inserted into the C-terminal hinge loop of the highly constrained enzyme RNase A, and tested for fibril growth and Congo red ... More
Protein fibrils termed amyloid-like are associated with numerous degenerative diseases as well as some normal cellular functions. Specific short segments of amyloid-forming proteins have been shown to form fibrils themselves. However, it has not been shown in general that these segments are capable of driving a protein from its native structure into the amyloid state. We applied the 3D profile method to identify fibril-forming segments within the amyloid-forming human proteins tau, alpha-synuclein, PrP prion and amyloid-beta. Ten segments, six to eight residues in length, were chosen and inserted into the C-terminal hinge loop of the highly constrained enzyme RNase A, and tested for fibril growth and Congo red birefringence. We find that all 10 unique inserts cause RNase A to form amyloid-like fibrils which display characteristic yellow to apple-green Congo red birefringence when observed with cross polarizers. These six to eight residue inserts can fibrillize RNase A and are sufficient for amyloid fibril spine formation.
