Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a Street, 02-106, Warsaw, Poland.
Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.
Protein J. 2022 Jun;41(3):361-368. doi: 10.1007/s10930-022-10056-7. Epub 2022 Jun 1.
Amyloid-β (Aβ) peptides are involved in Alzheimer's disease (AD) development. The interactions of these peptides with copper and zinc ions also seem to be crucial for this pathology. Although Cu(II) and Zn(II) ions binding by Aβ peptides has been scrupulously investigated, surprisingly, this phenomenon has not been so thoroughly elucidated for N-truncated Aβ-probably the most common version of this biomolecule. This negligence also applies to mixed Cu-Zn complexes. From the structural in silico analysis presented in this work, it appears that there are two possible mixed Cu-Zn(Aβ) complexes with different stoichiometries and, consequently, distinct properties. The Cu-Zn(Aβ) complex with 1:1:1 stoichiometry may have a neuroprotective superoxide dismutase-like activity. On the other hand, another mixed 2:1:2 Cu-Zn(Aβ) complex is perhaps a seed for toxic oligomers. Hence, this work proposes a novel research direction for our better understanding of AD development.
淀粉样蛋白-β（Aβ）肽参与阿尔茨海默病（AD）的发展。这些肽与铜和锌离子的相互作用似乎对这种病理学也至关重要。尽管 Aβ 肽与 Cu(II)和 Zn(II)离子的结合已被仔细研究，但令人惊讶的是，对于 N 截断的 Aβ（可能是这种生物分子最常见的版本），这一现象尚未得到如此彻底的阐明。这种疏忽也适用于混合 Cu-Zn 配合物。从本工作中呈现的结构计算分析来看，似乎存在两种具有不同化学计量比的可能的混合 Cu-Zn(Aβ)配合物，因此具有不同的性质。具有 1:1:1 化学计量比的 Cu-Zn(Aβ)配合物可能具有神经保护超氧化物歧化酶样活性。另一方面，另一种混合的 2:1:2 Cu-Zn(Aβ)配合物可能是有毒寡聚物的种子。因此，这项工作为我们更好地理解 AD 发展提出了一个新的研究方向。
