8FG6

Design of amyloidogenic peptide traps

8FG6 の概要

• エントリーDOI: 10.2210/pdb8fg6/pdb
• 分子名称: amyloidogenic peptide, C104.1 (3 entities in total)
• 機能のキーワード: de novo design, amyloidogenic peptide, beta-strand, amyloid fibrils, de novo protein
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 18161.41

構造登録者

Sahtoe, D.D.,Bera, A.K.,Baker, D. (登録日: 2022-12-12, 公開日: 2024-03-20, 最終更新日: 2024-08-07)

主引用文献

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

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: 38503834
DOI: 10.1038/s41589-024-01578-5

実験手法

X-RAY DIFFRACTION (2.3 Å)