Laboratory of Analytical Chemistry, Department of Chemistry, University of Helsinki, Helsinki, Finland.
J Phys Chem B. 2011 Apr 28;115(16):4818-25. doi: 10.1021/jp110987r. Epub 2011 Apr 1.
A force field has been previously designed for a dodecasaccharide chain of chondroitin-6-sulfate (C6S) and has proved to yield valuable data going from basic conformational properties to a more detailed H-bonding network. This force field is further used here to unravel the interaction of C6S with its pathological counterpart in low density lipoprotein (LDL) particles. In particular, well-selected peptide fragment p2 (residues 3359-3377) also identified as the principal proteoglycan binding site (PPBS) of the major protein in LDL, apolipoproteinB-100 (apoB-100), was chosen. We study here the interaction between C6S and p2. The role of arginine and lysine, positively charged amino acids of p2, in the crucial interaction of C6S with LDL is highlighted. The secondary structure of p2 is shown to affect the efficiency of the interaction, as the α-helical structure of p2 allows optimal interaction with C6S also in dynamic conditions. One point mutation in p2 appeared to affect consequently p2-C6S interaction.
先前已为硫酸软骨素-6 糖醛酸（C6S）的十二糖链设计了一个力场，事实证明，该力场可以提供从基本构象特性到更详细氢键网络的有价值数据。在此，我们进一步使用该力场来揭示 C6S 与 LDL 颗粒中其病理对应物的相互作用。特别是，选择了经过精心挑选的肽片段 p2（残基 3359-3377），它也被确定为 LDL 中主要蛋白质载脂蛋白 B-100（apoB-100）的主要蛋白聚糖结合位点（PPBS）。我们在这里研究 C6S 与 p2 之间的相互作用。强调了 p2 中带正电荷的精氨酸和赖氨酸在 C6S 与 LDL 关键相互作用中的作用。p2 的二级结构显示出影响相互作用效率的作用，因为 p2 的α-螺旋结构允许 p2 与 C6S 即使在动态条件下也能进行最佳相互作用。p2 中的一个点突变似乎随后影响了 p2-C6S 相互作用。
