Interdisciplinary Biotechnology Unit, Aligarh Muslim University Aligarh, UP, 202002, India.
Curr Protein Pept Sci. 2020;21(6):573-583. doi: 10.2174/1389203721666200204122732.
Protein folding is a natural phenomenon through which a linear polypeptide possessing necessary information attains three-dimension functionally active conformation. This is a complex and multistep process and therefore, the presence of several intermediary structures could be speculated as a result of protein folding. In in vivo, this folding process is governed by the assistance of other proteins called molecular chaperones and heat shock proteins. Due to the mechanism of protein folding, these intermediary structures remain major challenge for modern biology. Mutation in gene encoding amino acid can cause adverse environmental conditions which may result in misfolding of the linear polypeptide followed by the formation of aggregates and amyloidosis. Aggregation contributes to the pathophysiology of several maladies including diabetes mellitus, Huntington's and Alzheimer's disease. The propensity of native structure to form aggregated and fibrillar assemblies is a hallmark of amyloidosis. During aggregation of a protein, transition from α helix to β sheet is observed, and mainly β sheeted structure is visualised in a mature fibril. Heme proteins are very crucial for major life activities like transport of oxygen and carbon dioxide, synthesis of ATP, role in electron transport chain, and detoxification of free radicals formed during biochemical reactions. Any structural variation in the heme proteins may lead to a fatal response. Hence characterization of the folding intermediates becomes crucial. The characterization has been deciphered with the help of strong denaturants like acetonitrile and TFE. Moreover, possible role of elimination of these aggregates and prevention of protein denaturation is also discussed. Current review deals with the basic process and mechanism of the protein folding in general and the ultimate outcomes of the protein misfolding. Since Native conformation of heme proteins is essential for some vital activities as listed above, we have discussed possible prevention of denaturation and aggregation of heme proteins such as Hb, cyt c, catalase & peroxidase.
蛋白质折叠是一种自然现象，通过这种现象，具有必要信息的线性多肽获得三维功能活性构象。这是一个复杂的多步骤过程，因此，可以推测蛋白质折叠过程中存在几种中间结构。在体内，这个折叠过程受到称为分子伴侣和热休克蛋白的其他蛋白质的协助。由于蛋白质折叠的机制，这些中间结构仍然是现代生物学的主要挑战。编码氨基酸的基因突变会导致不利的环境条件，可能导致线性多肽错误折叠，随后形成聚集体和淀粉样变性。聚集导致包括糖尿病、亨廷顿氏病和阿尔茨海默病在内的几种疾病的病理生理学。天然结构形成聚集和纤维状组装的倾向是淀粉样变性的标志。在蛋白质聚集过程中，观察到从α螺旋到β片层的转变，并且在成熟的纤维中主要观察到β片层结构。血红素蛋白对于主要的生命活动非常重要，如氧气和二氧化碳的运输、ATP 的合成、电子传递链中的作用以及在生化反应中形成的自由基的解毒。血红素蛋白的任何结构变化都可能导致致命的反应。因此，折叠中间体的特征变得至关重要。该特征已借助于强变性剂（如乙腈和 TFE）得到了解释。此外，还讨论了消除这些聚集体和防止蛋白质变性的可能作用。目前的综述涉及蛋白质折叠的一般基本过程和机制以及蛋白质错误折叠的最终结果。由于血红素蛋白的天然构象对于上述一些重要活动是必需的，因此我们讨论了可能预防血红蛋白、细胞色素 c、过氧化氢酶和过氧化物酶等血红素蛋白的变性和聚集的方法。
