Role of glycosylation in structure and stability of Erythrina corallodendron lectin (EcorL): A molecular dynamics study
Role of glycosylation in structure and stability of Erythrina corallodendron lectin (EcorL): A molecular dynamics study
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DOI：
10.1002/pro.578
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发表时间：
2011-03-01
期刊：
影响因子：
8
通讯作者：
Surolia, Avadhesha
中科院分区：
文献类型：
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作者：
Kaushik, Sandeep;Mohanty, Debasisa;Surolia, Avadhesha
糖基化对糖蛋白结构和稳定性的影响一直是人们非常感兴趣的话题。在这项工作中，我们通过对糖基化刺桐凝集素（EcorL）和非糖基化重组刺桐凝集素（rEcorL）进行一系列长分子动力学（MD）模拟，研究了寡糖的溶液构象及其对糖蛋白结构和稳定性的影响。我们的结果表明，尽管整体三维结构相似，但与非糖基化 EcorL 相比，糖基化 EcorL 具有较小的非极性溶剂可及表面积。这可能解释了实验观察到糖基化 EcorL 比非糖基化 EcorL 具有更高的热力学稳定性。模拟结果分析表明，蛋白质残基与寡糖之间相互作用的动态视图与晶体结构中看到的静态图像完全不同。寡糖部分与 Lys 55 和 Tyr 53 具有动态稳定的相互作用，这两个氨基酸均按顺序与糖基化位点 Asn 17 分开。糖基化可能有助于在氨基酸之间形成长程接触，这些氨基酸按顺序分开，从而提供折叠核。因此，我们的模拟不仅揭示了寡糖采样的构象，而且还提供了对可能的分子机制的新见解，通过该分子机制，糖基化可以通过形成涉及与寡糖部分的特定接触的折叠核来帮助糖蛋白的折叠。
The effect of glycosylation on structure and stability of glycoproteins has been a topic of considerable interest. In this work, we have investigated the solution conformation of the oligosaccharide and its effect on the structure and stability of the glycoprotein by carrying out a series of long Molecular dynamics (MD) simulations on glycosylated Erythrina corallodendron lectin (EcorL) and nonglycosylated recombinant Erythrina corallodendron lectin (rEcorL). Our results indicate that, despite the similarity in overall three dimensional structures, glycosylated EcorL has lesser nonpolar solvent accessible surface area compared to nonglycosylated EcorL. This might explain the experimental observation of higher thermodynamic stability for glycosylated EcorL compared to nonglycosylated EcorL. Analysis of the simulation results indicates that, dynamic view of interactions between protein residues and oligosaccharide is entirely different from the static picture seen in the crystal structure. The oligosaccharide moiety had dynamically stable interactions with Lys 55 and Tyr 53, both of which are separated in sequence from the site of glycosylation, Asn 17. It is possible that glycosylation helps in forming long-range contacts between amino acids, which are separated in sequence and thus provides a folding nucleus. Thus our simulations not only reveal the conformations sampled by the oligosaccharide, but also provide novel insights into possible molecular mechanisms by which glycosylation can help in folding of the glycoprotein by formation of folding nucleus involving specific contacts with the oligosaccharide moiety.