Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati, Assam, India.
Adv Protein Chem Struct Biol. 2011;84:63-111. doi: 10.1016/B978-0-12-386483-3.00003-3.
Ever since lysozyme was discovered by Fleming in 1922, this protein has emerged as a model for investigations on protein structure and function. Over the years, several high-resolution structures have yielded a wealth of structural data on this protein. Extensive studies on folding of lysozyme have shown how different regions of this protein dynamically interact with one another. Data is also available from numerous biotechnological studies wherein lysozyme has been employed as a model protein for recovering active recombinant protein from inclusion bodies using small molecules like l-arginine. A variety of conditions have been developed in vitro to induce fibrillation in hen lysozyme. They include (a) acidic pH at elevated temperature, (b) concentrated solutions of ethanol, (c) moderate concentrations of guanidinium hydrochloride at moderate temperature, and (d) alkaline pH at room temperature. This review aims to bring together similarities and differences in aggregation mechanisms, morphology of aggregates, and related issues that arise using the different conditions mentioned above to improve our understanding. The alkaline pH condition (pH 12.2), discovered and studied extensively in our lab, shall receive special attention. More than a decade ago, it was revealed that mutations in human lysozyme can cause accumulation of large quantities of amyloid in liver, kidney, and other regions of gastrointestinal tract. Understanding the mechanism of lysozyme aggregation will probably have therapeutic implications for the treatment of systemic nonneuropathic amyloidosis. Numerous studies have begun to focus attention on inhibition of lysozyme aggregation using antibody or small molecules. The enzymatic activity of lysozyme presents a convenient handle to quantify the native population of lysozyme in a sample where aggregation has been inhibited. The rich information available on lysozyme coupled with the multiple conditions that have been successful in inducing/inhibiting its aggregation in vitro makes lysozyme an ideal model protein to investigate amyloidogenesis.
自弗莱明于 1922 年发现溶菌酶以来，这种蛋白质已成为研究蛋白质结构和功能的模型。多年来，已有几种高分辨率结构产生了大量有关该蛋白质的结构数据。对溶菌酶折叠的广泛研究表明，该蛋白质的不同区域如何动态地相互作用。在许多生物技术研究中也有数据可用，其中溶菌酶被用作从包涵体中回收活性重组蛋白的模型蛋白，使用小分子如精氨酸。已经开发了各种体外条件来诱导鸡溶菌酶的纤维化。它们包括(a)高温下的酸性 pH 值，(b)乙醇的浓缩溶液，(c)中温和的盐酸胍浓度在中等温度下，和(d)室温下的碱性 pH 值。本综述旨在汇集使用上述不同条件引起的聚集机制、聚集体形态和相关问题的异同，以提高我们的理解。碱性 pH 值条件（pH 12.2）是在我们实验室中发现并广泛研究的，将受到特别关注。十多年前，人们发现人溶菌酶的突变会导致肝脏、肾脏和胃肠道其他区域大量淀粉样蛋白的积累。了解溶菌酶聚集的机制可能对治疗全身性非神经淀粉样变性具有治疗意义。许多研究已经开始关注使用抗体或小分子抑制溶菌酶聚集。溶菌酶的酶活性提供了一个方便的处理方法，可以定量测定抑制聚集的样品中天然溶菌酶的含量。与在体外成功诱导/抑制其聚集的多种条件相结合，丰富的溶菌酶信息使溶菌酶成为研究淀粉样变性的理想模型蛋白。
