2MGT

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

Summary for 2MGT

• Entry DOI: 10.2210/pdb2mgt/pdb
• NMR Information: BMRB: 19602
• Descriptor: Amyloid beta A4 protein, ZINC ION (2 entities in total)
• Functional Keywords: alzheimer's disease, human amyloid -peptide, zinc binding, protein fibril, metal binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 4071.69

Authors

Polshakov, V.,Istrate, A.,Kozin, S. (deposition date: 2013-11-06, release date: 2014-11-12, Last modification date: 2024-10-30)

Primary citation

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

Experimental method

SOLUTION NMR