2otk
From Proteopedia
Structure of Alzheimer Ab peptide in complex with an engineered binding protein
Overview
According to the amyloid hypothesis, the pathogenesis of Alzheimer's disease is triggered by the oligomerization and aggregation of the amyloid-beta (Abeta) peptide into protein plaques. Formation of the potentially toxic oligomeric and fibrillar Abeta assemblies is accompanied by a conformational change toward a high content of beta-structure. Here, we report the solution structure of Abeta(1-40) in complex with the phage-display selected affibody protein Z(Abeta3), a binding protein of nanomolar affinity. Bound Abeta(1-40) features a beta-hairpin comprising residues 17-36, providing the first high-resolution structure of Abeta in beta conformation. The positions of the secondary structure elements strongly resemble those observed for fibrillar Abeta. Z(Abeta3) stabilizes the beta-sheet by extending it intermolecularly and by burying both of the mostly nonpolar faces of the Abeta hairpin within a large hydrophobic tunnel-like cavity. Consequently, Z(Abeta3) acts as a stoichiometric inhibitor of Abeta fibrillation. The selected Abeta conformation allows us to suggest a structural mechanism for amyloid formation based on soluble oligomeric hairpin intermediates.
About this Structure
2OTK is a Single protein structure of sequence from Homo sapiens and Engineered binding protein. Full crystallographic information is available from OCA.
Reference
Stabilization of a beta-hairpin in monomeric Alzheimer's amyloid-beta peptide inhibits amyloid formation., Hoyer W, Gronwall C, Jonsson A, Stahl S, Hard T, Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5099-104. Epub 2008 Mar 28. PMID:18375754 Page seeded by OCA on Thu Apr 24 09:26:03 2008
