2OTK
Structure of Alzheimer Ab peptide in complex with an engineered binding protein
Summary for 2OTK
| Entry DOI | 10.2210/pdb2otk/pdb |
| Descriptor | Amyloid beta A4 protein, ZAb3 Affibody dimer (2 entities in total) |
| Functional Keywords | protein-peptide complex, beta-hairpin, intermolecular beta-sheet, de novo protein, peptide binding protein |
| Biological source | engineered binding protein More |
| Total number of polymer chains | 3 |
| Total formula weight | 19967.09 |
| Authors | |
| Primary citation | Hoyer, W.,Gronwall, C.,Jonsson, A.,Stahl, S.,Hard, T. Stabilization of a beta-hairpin in monomeric Alzheimer's amyloid-beta peptide inhibits amyloid formation. Proc.Natl.Acad.Sci.Usa, 105:5099-5104, 2008 Cited by PubMed Abstract: 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. PubMed: 18375754DOI: 10.1073/pnas.0711731105 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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