Bashir Sania, Shamsi Anas, Ahmad Faizan, Hassan Md Imtaiyaz, Kamal Mohammad Azhar, Islam Asimul
Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
Department of Biochemistry, College of Science, University of Jeddah, Jeddah 21589, Saudi Arabia.
ACS Omega. 2020 Oct 8;5(41):26871-26882. doi: 10.1021/acsomega.0c04062. eCollection 2020 Oct 20.
Protein aggregation is among the most challenging new frontiers in protein chemistry as well as in molecular medicine and has direct implications in protein misfolding. This study investigated the role of sugar molecules (glucose, fructose, sucrose, and the mixture of glucose and fructose) in protecting the structural integrity of α-lactalbumin (α-LA) against aggregation. The research focused here is the inhibitory capabilities of sugars against α-LA fibril formation investigated employing diverse multispectroscopic and microscopic techniques. The aggregation was induced in α-LA thermally with a change in concentration. UV-vis spectroscopy, ThT binding assay, Trp fluorescence, Rayleigh scattering, and turbidity assay depicted synchronized results. Further, transmission electron microscopy (TEM) complemented that a mixture of glucose and fructose was the best inhibitor of α-LA fibril formation. Inhibition of α-LA aggregation by sugar osmolytes is attributed to the formation of hydrogen bonds between these osmolytes, as evidenced by the molecular docking results. This hydrogen bonding is a key player that prevents aggregation in α-LA in the presence of sugar osmolytes. This study provides an insight into the ability of naturally occurring sugar osmolytes to inhibit fibril formation and can serve as a platform to treat protein misfolding and aggregation-oriented disorders.
蛋白质聚集是蛋白质化学以及分子医学中最具挑战性的新领域之一，并且与蛋白质错误折叠直接相关。本研究调查了糖分子（葡萄糖、果糖、蔗糖以及葡萄糖和果糖的混合物）在保护α-乳白蛋白（α-LA）结构完整性以防止聚集方面的作用。这里所关注的研究是利用多种多光谱和显微镜技术研究糖类对α-LA纤维形成的抑制能力。通过改变浓度以热诱导α-LA发生聚集。紫外可见光谱、硫代黄素T结合试验、色氨酸荧光、瑞利散射和浊度测定呈现出同步的结果。此外，透射电子显微镜（TEM）补充表明葡萄糖和果糖的混合物是α-LA纤维形成的最佳抑制剂。分子对接结果表明，糖类渗透剂对α-LA聚集的抑制作用归因于这些渗透剂之间形成了氢键。这种氢键是在存在糖类渗透剂的情况下防止α-LA聚集的关键因素。本研究深入了解了天然存在的糖类渗透剂抑制纤维形成的能力，并可作为治疗蛋白质错误折叠和聚集相关疾病的平台。
