The English (H6R) familial Alzheimer's disease mutation facilitates zinc-induced dimerization of the amyloid-β metal-binding domain

S. A. Kozin; A. A. Kulikova; A. N. Istrate; P. O. Tsvetkov; S. S. Zhokhov; Y. V. Mezentsev; O. I. Kechko; A. S. Ivanov; V. I. Polshakov; A. A. Makarov

doi:10.1039/C4MT00259H

The English (H6R) familial Alzheimer's disease mutation facilitates zinc-induced dimerization of the amyloid-β metal-binding domain†

S. A. Kozin,‡^a A. A. Kulikova,‡^a A. N. Istrate,‡^a P. O. Tsvetkov,^a S. S. Zhokhov,^b Y. V. Mezentsev,^c O. I. Kechko,^a A. S. Ivanov,^c V. I. Polshakov^d and A. A. Makarov*^a

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* Corresponding authors

^a Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov street 32, 119991 Moscow, Russia
E-mail: aamakarov@eimb.ru

^b Chemistry Department, M.V. Lomonosov Moscow State University, 119191 Moscow, Russia

^c Institute of Biomedical Chemistry, Pogodinskaya street 10/8, 119121 Moscow, Russia

^d Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University, 119191 Moscow, Russia

Abstract

Interaction of Zn²⁺ with the metal-binding domain of the English (H6R) amyloid-β mutant results in the formation of peptide dimers. The mutation causes the exclusion of His6 from the zinc chelation pattern observed in the intact domain and triggers the assembly of the dimers via zinc ions coordinated by ¹¹EVHH¹⁴ fragments.

This article is part of the themed collections: Zinc in the Biosciences and Alzheimer's Research Month 2016

Metallomics

The English (H6R) familial Alzheimer's disease mutation facilitates zinc-induced dimerization of the amyloid-β metal-binding domain†

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