8FG6
Design of amyloidogenic peptide traps
Summary for 8FG6
| Entry DOI | 10.2210/pdb8fg6/pdb |
| Descriptor | amyloidogenic peptide, C104.1 (3 entities in total) |
| Functional Keywords | de novo design, amyloidogenic peptide, beta-strand, amyloid fibrils, de novo protein |
| Biological source | synthetic construct More |
| Total number of polymer chains | 2 |
| Total formula weight | 18161.41 |
| Authors | Sahtoe, D.D.,Bera, A.K.,Baker, D. (deposition date: 2022-12-12, release date: 2024-03-20, Last modification date: 2024-08-07) |
| Primary citation | Sahtoe, D.D.,Andrzejewska, E.A.,Han, H.L.,Rennella, E.,Schneider, M.M.,Meisl, G.,Ahlrichs, M.,Decarreau, J.,Nguyen, H.,Kang, A.,Levine, P.,Lamb, M.,Li, X.,Bera, A.K.,Kay, L.E.,Knowles, T.P.J.,Baker, D. Design of amyloidogenic peptide traps. Nat.Chem.Biol., 20:981-990, 2024 Cited by PubMed Abstract: Segments of proteins with high β-strand propensity can self-associate to form amyloid fibrils implicated in many diseases. We describe a general approach to bind such segments in β-strand and β-hairpin conformations using de novo designed scaffolds that contain deep peptide-binding clefts. The designs bind their cognate peptides in vitro with nanomolar affinities. The crystal structure of a designed protein-peptide complex is close to the design model, and NMR characterization reveals how the peptide-binding cleft is protected in the apo state. We use the approach to design binders to the amyloid-forming proteins transthyretin, tau, serum amyloid A1 and amyloid β (Aβ42). The Aβ binders block the assembly of Aβ fibrils as effectively as the most potent of the clinically tested antibodies to date and protect cells from toxic Aβ42 species. PubMed: 38503834DOI: 10.1038/s41589-024-01578-5 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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