2MGT

Zinc induced dimer of the metal binding domain 1-16 of human amyloid beta-peptide with Alzheimer's disease pathogenic English mutation H6R

2MGT の概要

• エントリーDOI: 10.2210/pdb2mgt/pdb
• NMR情報: BMRB: 19602
• 分子名称: Amyloid beta A4 protein, ZINC ION (2 entities in total)
• 機能のキーワード: alzheimer's disease, human amyloid -peptide, zinc binding, protein fibril, metal binding protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 4071.69

構造登録者

Polshakov, V.,Istrate, A.,Kozin, S. (登録日: 2013-11-06, 公開日: 2014-11-12, 最終更新日: 2024-10-30)

主引用文献

Istrate, A.N.,Kozin, S.A.,Zhokhov, S.S.,Mantsyzov, A.B.,Kechko, O.I.,Pastore, A.,Makarov, A.A.,Polshakov, V.I.
Interplay of histidine residues of the Alzheimer's disease A beta peptide governs its Zn-induced oligomerization.
Sci Rep, 6:21734-21734, 2016

PubMed Abstract: Conformational changes of Aβ peptide result in its transformation from native monomeric state to the toxic soluble dimers, oligomers and insoluble aggregates that are hallmarks of Alzheimer's disease (AD). Interactions of zinc ions with Aβ are mediated by the N-terminal Aβ(1-16) domain and appear to play a key role in AD progression. There is a range of results indicating that these interactions trigger the Aβ plaque formation. We have determined structure and functional characteristics of the metal binding domains derived from several Aβ variants and found that their zinc-induced oligomerization is governed by conformational changes in the minimal zinc binding site 6HDSGYEVHH14. The residue H6 and segment 11EVHH14, which are part of this site are crucial for formation of the two zinc-mediated interaction interfaces in Aβ. These structural determinants can be considered as promising targets for rational design of the AD-modifying drugs aimed at blocking pathological Aβ aggregation.

PubMed: 26898943
DOI: 10.1038/srep21734

実験手法

SOLUTION NMR