Short protein segments can drive a non-fibrillizing protein into the amyloid state.
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.
Teng
Poh K
PK
Department 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.
Eisenberg
David
D
D000682:Amyloid / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D016229:Amyloid beta-Peptides / Q000235:genetics; D000818:Animals; D002417:Cattle; D006801:Humans; D008854:Microscopy, Electron; D008958:Models, Molecular; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D011328:Prions / Q000235:genetics; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012259:Ribonuclease, Pancreatic / Q000235:genetics / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics; D016875:tau Proteins / Q000235:genetics
D000682:Amyloid; D016229:Amyloid beta-Peptides; C054369:MAPT protein, human; D010446:Peptide Fragments; D011328:Prions; D011993:Recombinant Fusion Proteins; D051844:alpha-Synuclein; D016875:tau Proteins; D012259:Ribonuclease, Pancreatic