In-silico structural analysis of Heterocephalus glaber amyloid beta: an anti-Alzheimer's peptide.

IF 1.5 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Ali Javanmard, Maryam Azimzadeh-Irani, Ghazal Tafazzoli, Ayla Esmaeilzadeh, Mohammad Shirinpoor-Kharf, Seyyed Mohammad Hasan Haghayeghi
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引用次数: 0

Abstract

Heterocephalus glaber, known as the Naked mole-rat, has an extraordinary immunity to Alzheimer's disease. The pathological hallmark of Alzheimer's disease is cerebral accumulations of plaques, consisting of self-aggregated amyloid beta peptides. Homo sapiens and H. glaber amyloid beta peptides are different in only one amino acid. Herein, computational structural analyses were carried out to determine whether plaque development in H. glaber is prevented by the replacement of His13 with Arg13 in the amyloid beta peptide. AlphaFold2 was used to predict the structure of the H. glaber amyloid beta peptide. HADDOCK and Hex were used to self-dock the peptides and dock ions on peptides, respectively. Illustrations were made by PyMol and ChimeraX. Using VMD, we calculated the radius of gyration. The phylogenetic analysis was conducted by Mega. The results showed an accurate structure with two alpha helices separated by a short coil for H. glaber. Self-docking of the two amyloid beta peptides demonstrated a globular conformation in the H. glaber dimer, implying the unlikeliness of amyloid beta peptides' self-aggregation to form fibrillar structures. This conformational state resulted in lower electrostatic energy compared to H. sapiens, contributing to H. glaber's lower tendency for fibril and, ultimately, plaque formation. Phylogenetic analysis confirmed that amyloid precursor protein is highly conserved in each taxon of rodentia and primata. This study provides insight into the connection between the structure of H. glaber amyloid beta and its plaque formation properties, showing that the Arg13 in H. glaber leads to fibril instability, and might prevent senile plaque accumulation.

褐藻淀粉样蛋白 beta:一种抗老年痴呆症肽的分子内结构分析。
被称为 "裸鼹鼠 "的 Heterocephalus glaber 对阿尔茨海默病具有超乎寻常的免疫力。阿尔茨海默氏症的病理特征是大脑积聚斑块,由自我聚集的淀粉样 beta 肽组成。智人和格拉伯人的β淀粉样肽只有一个氨基酸不同。在此,我们进行了计算结构分析,以确定用 Arg13 取代淀粉样 beta 肽中的 His13 是否能阻止 H. glaber 中斑块的形成。使用 AlphaFold2 预测了草履虫淀粉样 beta 肽的结构。HADDOCK 和 Hex 分别用于肽的自对接和肽上离子的对接。插图由 PyMol 和 ChimeraX 绘制。我们使用 VMD 计算了回旋半径。系统进化分析由 Mega 进行。结果表明,H. glaber 的结构准确,两个α螺旋之间有一个短线圈隔开。两种淀粉样β肽的自我对接表明,H. glaber二聚体中的淀粉样β肽呈球状构象,这意味着淀粉样β肽不可能自我聚集形成纤维状结构。与 H. sapiens 相比,这种构象状态产生的静电能量更低,从而使 H. glaber 更倾向于形成纤维,并最终形成斑块。系统发育分析证实,淀粉样前体蛋白在啮齿类动物和灵长类动物的各个类群中高度保守。这项研究深入探讨了草履虫淀粉样蛋白 beta 的结构与其斑块形成特性之间的联系,表明草履虫中的 Arg13 会导致纤维的不稳定性,并可能阻止老年斑块的积累。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Molecular Biology Research Communications
Molecular Biology Research Communications BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
3.00
自引率
0.00%
发文量
12
期刊介绍: “Molecular Biology Research Communications” (MBRC) is an international journal of Molecular Biology. It is published quarterly by Shiraz University (Iran). The MBRC is a fully peer-reviewed journal. The journal welcomes submission of Original articles, Short communications, Invited review articles, and Letters to the Editor which meets the general criteria of significance and scientific excellence in all fields of “Molecular Biology”.
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