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Protein Eng Des Sel. 2009 Aug;22(8):531-6. doi: 10.1093/protein/gzp037. Epub 2009 Jul 14.

Short protein segments can drive a non-fibrillizing protein into the amyloid state.

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  • 1Department of Biological Chemistry, UCLA-DOE Institute for Genomics and Proteomics, Howard Hughes Medical Institute, Molecular Biology Institute, UCLA, Box 951570, Los Angeles, CA 90095-1570, USA.

Abstract

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.

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