Department of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences, Watsonova 47, 040 01 Kosice, Slovakia.
Center for Interdisciplinary Biosciences, Technology and Innovation Park, P. J. Safarik University, Jesenna 5, 040 01 Kosice, Slovakia.
Colloids Surf B Biointerfaces. 2021 Jan;197:111428. doi: 10.1016/j.colsurfb.2020.111428. Epub 2020 Oct 23.
Amphiphilic compounds, both detergents and lipids, are important tools for in vitro analysis of water-soluble and integral membrane proteins. A key question is whether these two groups of amphiphilic molecules use the same pathway to affect structural and functional integrity of proteins. In the present study, we tested the effect of non-ionic detergent dodecyl maltoside (DDM), two phospholipids, 1,2-dimyristoyl-sn-glycero-3- phosphocholine (DMPC), 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC), and the detergent-phospholipid mixtures on insulin amyloidogenesis in vitro. Amyloidogenesis of insulin is significantly affected by DDM in a time-and dose-dependent manner, but only slightly affected by either of phospholipids. Addition of DHPC or DMPC to detergent does not alter the inhibiting pattern, suggesting that DDM preferably binds to insulin. The molecular modeling revealed that DDM and the phospholipids occupy equivalent binding sites. DDM, due to the presence of maltose with several oxygen atoms (hydroxylic, glycosidic and ring) is involved in more hydrogen bonds than DHPC or DMPC. Hydrophobic interactions are important factors to stabilize both, DDM and phospholipids in their binding sites. Our results indicate that certain detergents (applying DDM as an example) and selected phospholipids are not always interchangeable in their use to investigate the effect of amphiphilic compounds on the behavior of amyloid-prone proteins.
两亲化合物，包括清洁剂和脂质，是用于体外分析水溶性和整合膜蛋白的重要工具。一个关键问题是这两组两亲分子是否使用相同的途径来影响蛋白质的结构和功能完整性。在本研究中，我们测试了非离子清洁剂十二烷基麦芽糖（DDM）、两种磷脂，1,2-二肉豆蔻酰-sn-甘油-3-磷酸胆碱（DMPC）、1,2-二己酰基-sn-甘油-3-磷酸胆碱（DHPC）以及清洁剂-磷脂混合物对胰岛素体外淀粉样变性的影响。DDM 以时间和剂量依赖的方式显著影响胰岛素的淀粉样变性，但对任何一种磷脂的影响都很小。向清洁剂中添加 DHPC 或 DMPC 不会改变抑制模式，表明 DDM 更倾向于与胰岛素结合。分子建模表明，DDM 和磷脂占据等效的结合位点。由于麦芽糖具有几个氧原子（羟基、糖苷和环），DDM 比 DHPC 或 DMPC 参与更多的氢键。疏水相互作用是稳定 DDM 和磷脂在其结合位点中的重要因素。我们的结果表明，某些清洁剂（以 DDM 为例）和选定的磷脂在用于研究两亲化合物对淀粉样蛋白倾向蛋白行为的影响时并不总是可以互换使用。
