Structural highlights
Publication Abstract from PubMed
Zinc-induced oligomerization of amyloid-beta peptide (Abeta) produces potentially pathogenic agents of Alzheimer's disease. Mutations and modifications in the metal binding domain 1-16 of Abeta peptide crucially affect its zinc-induced oligomerization by changing intermolecular zinc mediated interface. The 3D structure of this interface appearing in a range of Abeta species is a prospective drug target for disease modifying therapy. Using NMR spectroscopy, EXAFS spectroscopy, mass spectrometry, and isothermal titration calorimetry the interaction of zinc ions with Abeta fragments 1-7 and 1-10 carrying familial Taiwanese mutation D7H was studied. Zinc ions induce formation of a stable homodimer formed by the two peptide chains fastened by two zinc ions and stacking interactions of imidazole rings. A binuclear zinc interaction fold in the dimer structure was discovered. It can be used for designing zinc-regulated proteins and zinc-mediated self-assembling peptides.
A Binuclear Zinc Interaction Fold Discovered in the Homodimer of Alzheimer's Amyloid-beta Fragment with Taiwanese Mutation D7H.,Polshakov VI, Mantsyzov AB, Kozin SA, Adzhubei AA, Zhokhov SS, van Beek W, Kulikova AA, Indeykina MI, Mitkevich VA, Makarov AA Angew Chem Int Ed Engl. 2017 Jun 1. doi: 10.1002/anie.201704615. PMID:28570778[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Polshakov VI, Mantsyzov AB, Kozin SA, Adzhubei AA, Zhokhov SS, van Beek W, Kulikova AA, Indeykina MI, Mitkevich VA, Makarov AA. A Binuclear Zinc Interaction Fold Discovered in the Homodimer of Alzheimer's Amyloid-beta Fragment with Taiwanese Mutation D7H. Angew Chem Int Ed Engl. 2017 Jun 1. doi: 10.1002/anie.201704615. PMID:28570778 doi:http://dx.doi.org/10.1002/anie.201704615
