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Zinc-induced heterodimer formation between metal-binding domains of intact and naturally modified amyloid-beta species: implication to amyloid seeding in Alzheimer’s disease?статья
Дата последнего поиска статьи во внешних источниках: 18 марта 2016 г.
- Авторы: Mezentsev Yu, Medvedev A.E., Kechko O.I., Makarov A.A., Ivanov A.S., Mantsyzov A.B., Kozin S.A.
- Журнал: Journal of Biomolecular Structure and Dynamics
- Том: 34
- Номер: 11
- Год издания: 2016
- Издательство: Adenine Press
- Местоположение издательства: United States
- Первая страница: 2317
- Последняя страница: 2326
- DOI: 10.1080/07391102.2015.1113890
- Аннотация: Zinc ions and modified amyloid-beta peptides (Aβ) play a critical role in the pathological aggregation of endogenous Aβ in Alzheimer’s disease (AD). Zinc-induced Aβ oligomerization is mediated by the metal-binding domain (MBD) which includes N-terminal residues 1-16 (Aβ1-16). Earlier, it has been shown that Aβ1-16 as well as some of its naturally occurring variants undergoes zinc-induced homodimerization via the interface in which zinc ion is coordinated by Glu11 and His14 of the interacting subunits. In this study using surface plasmon resonance technique we have found that in the presence of zinc ions Aβ1-16 forms heterodimers with MBDs of two Aβ species linked to AD: Aβ containing isoAsp7 (isoAβ) and Aβ containing phosphorylated Ser8 (pS8-Aβ). The heterodimers appear to possess the same interface as the homodimers. Simulation of 200 ns molecular dynamic trajectories in two constructed models of dimers ([Aβ1-16/Zn/Aβ1-16] and [isoAβ1-16/Zn/Aβ1-16], has shown that conformational flexibility of the N-terminal fragments of the dimer subunits is controlled by the structure of corresponding sites 6-8. The data suggest that isoAβ and pS8-Aβ can be involved in the AD pathogenesis by means of their zinc-dependent interactions with endogenous Aβ resulting in formation of heterodimeric seeds for amyloid aggregation.
- Добавил в систему: Манцызов Алексей Борисович