Dynamics simulation of soybean agglutinin (SBA) dimer reveals the impact of glycosylation on its enhanced structural stability
Dynamics simulation of soybean agglutinin (SBA) dimer reveals the impact of glycosylation on its enhanced structural stability
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DOI：
10.1016/j.carres.2016.04.009
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发表时间：
2016-06-16
影响因子：
3.1
通讯作者：
Mukhopadhyay, Chaitali
中科院分区：
文献类型：
--
作者：
Halder, Swagata;Surolia, Avadhesha;Mukhopadhyay, Chaitali
豆科植物凝集素被广泛用作研究蛋白质-碳水化合物和蛋白质-蛋白质相互作用的模型系统。它们表现出迷人的四级结构变化。最近，已经清楚凝集素以寡聚体形式存在。大豆凝集素是一种四聚体的豆类凝集素，其每个亚基都是糖基化的。本文探讨了大豆凝集素二聚体稳定性的主要来源。为了了解糖基化对二聚体界面的作用，我们进行了正常（298 K），高温（380 K，500 K）长显式溶剂分子动力学（MD）模拟，并比较了糖基化和非糖基化二聚体之间的结构和构象变化。研究表明，在常温下的高度稳定性主要是由极性残基如Lys、Arg、Asp、Thr、Ser、Asn和Gln（62%）之间的界面离子相互作用（类似于200 kcal/mol）贡献的。它保持其整体折叠构象，由于在非典型界面的高亚基相互作用。主要是一个亚基的一个β折叠的C=O与另一个亚基的另一个β链的N-H之间的五个重要氢键有助于保持结构完整性。在非经典界面上，Arg 185-Asp 192、Lys 163-Asp 169、Asp 169-Lys 163和Asp 192-Arg 185之间的10个亚基间盐桥相互作用对维持SBA二聚体的三维结构具有重要作用。此外，我们的模拟结果表明，增加振动熵可以降低自由能，并有助于聚糖诱导的稳定化，在常温下约为45 kcal/mol。(C)2016爱思唯尔有限公司版权所有
The legume lectins are widely used as a model system for studying protein-carbohydrate and protein-protein interactions. They exhibit a fascinating quaternary structure variation. Recently, it has become clear that lectins exist as oligomers. Soybean agglutinin is a tetrameric legume lectin, each of whose sub-units are glycosylated. In the present study we explore the main origin for the stability of soybean agglutinin dimer. In order to understand the role of glycosylation on the dimeric interface, we have carried out normal (298K), high temperatures (380K, 500K) long explicit solvent molecular dynamics (MD) simulations and compared the structural and conformational changes between the glycosylated and non-glycosylated dimers. The study reveals that the high degree of stability at normal temperature is mostly contributed by interfacial ionic interactions (similar to 200 kcal/mol) between polar residues like Lys, Arg, Asp, Thr, Ser, Asn and Gln (62%). It maintains its overall folded conformation due to high subunit interactions at the non-canonical interface. Mainly five important hydrogen bonds between C=O of one beta sheet of one subunit with the N-H of other beta strand of the other subunit help to maintain the structural integrity. Ten inter subunit salt-bridge interactions between Arg 185-Asp192, Lys 163-Asp169, Asp 169-Lys 163 and Asp 192-Arg 185 at non-canonical interface appear to be important to maintain the three dimensional structure of SBA dimer. Moreover, our simulation results revealed that increase in vibrational entropy could decrease the free energy and contribute to the glycan-induced stabilization by similar to 45 kcal/mol at normal temperature. (C) 2016 Elsevier Ltd. All rights reserved.