Alteration of Biomolecular Conformation by Aluminum-Implications for Protein Misfolding Disease.
Alteration of Biomolecular Conformation by Aluminum-Implications for Protein Misfolding Disease.
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DOI：
10.3390/molecules27165123
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发表时间：
2022-08-11
期刊：
影响因子：
4.6
通讯作者：
Lukiw, Walter J.
中科院分区：
文献类型：
--
作者：
Zhao, Yuhai;Pogue, Aileen, I;Alexandrov, Peter N.;Butler, Leslie G.;Li, Wenhong;Jaber, Vivian R.;Lukiw, Walter J.
关键词：
天然元素铝具有许多独特的生化和生物物理特性，使这种高度神经毒性的物种对几种重要生物分子的结构完整性、构象、反应性和稳定性有害。这包括铝的(1)小的离子尺寸和高度亲电性，具有最高的电荷密度的任何金属阳离子的Z2/r为18（离子电荷+3，半径0.5 nm）；（ii）形成具有共价倾向的极其稳定的静电键的倾向；（iii）不可逆相互作用和/或显著减缓复杂铝-生物分子相互作用的交换速率的能力；（iv）极密的电正电荷，对供氧配体（如磷酸盐）具有已知的最高亲和力之一；（五）作为地球生物圈中最丰富的金属存在，并在饮用水、食品、药品、消费品、地下水和大气尘埃中普遍具有生物可利用性；（六）丰度是细胞内和细胞外最常见的金属毒素之一。尽管铝在生物圈中普遍存在且含量丰富，但它对所有动植物物种的耐受性都非常好；目前还不知道有什么生物会代谢铝；然而，铝在染色质压实中的生物学作用已被确定。在本通讯中，给出了几个例子，其中铝已被证明不可逆地干扰和/或稳定生物分子的自然构象，已知这些生物分子在能量代谢、基因表达、细胞稳态和神经疾病的病理信号传导中是重要的。包括牛头病、阿尔茨海默病和多种朊病毒疾病在内的几种神经退行性疾病涉及自然发生的细胞蛋白质构象的改变。根据目前可用的数据，我们推测铝导致神经系统疾病的一种方式是诱导自然发生的蛋白质错误折叠成改变的病理构型，从而导致神经退行性疾病的过程。
The natural element aluminum possesses a number of unique biochemical and biophysical properties that make this highly neurotoxic species deleterious towards the structural integrity, conformation, reactivity and stability of several important biomolecules. These include aluminum’s (i) small ionic size and highly electrophilic nature, having the highest charge density of any metallic cation with a Z2/r of 18 (ionic charge +3, radius 0.5 nm); (ii) inclination to form extremely stable electrostatic bonds with a tendency towards covalency; (iii) ability to interact irreversibly and/or significantly slow down the exchange-rates of complex aluminum–biomolecular interactions; (iv) extremely dense electropositive charge with one of the highest known affinities for oxygen-donor ligands such as phosphate; (v) presence as the most abundant metal in the Earth’s biosphere and general bioavailability in drinking water, food, medicines, consumer products, groundwater and atmospheric dust; and (vi) abundance as one of the most commonly encountered intracellular and extracellular metallotoxins. Despite aluminum’s prevalence and abundance in the biosphere it is remarkably well-tolerated by all plant and animal species; no organism is known to utilize aluminum metabolically; however, a biological role for aluminum has been assigned in the compaction of chromatin. In this Communication, several examples are given where aluminum has been shown to irreversibly perturb and/or stabilize the natural conformation of biomolecules known to be important in energy metabolism, gene expression, cellular homeostasis and pathological signaling in neurological disease. Several neurodegenerative disorders that include the tauopathies, Alzheimer’s disease and multiple prion disorders involve the altered conformation of naturally occurring cellular proteins. Based on the data currently available we speculate that one way aluminum contributes to neurological disease is to induce the misfolding of naturally occurring proteins into altered pathological configurations that contribute to the neurodegenerative disease process.
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DOI：
10.3390/molecules26103011
发表时间：
2021-05-18
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
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发表时间：
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影响因子：
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作者：
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影响因子：
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