Journal
PROTEIN ENGINEERING DESIGN & SELECTION
Volume 22, Issue 8, Pages 531-536Publisher
OXFORD UNIV PRESS
DOI: 10.1093/protein/gzp037
Keywords
amyloid; domain swapping; functional networks; prion structure; protein interactions
Funding
- National Science Foundation [MCB-0445429]
- National Institute on Aging [1R01 AG029430]
- United States Department of Energy Office of Biological and Environmental Research
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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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