DePaul University, 243 South Wabash Ave., Chicago, IL 60604-6116, United States.
Beckman Institute, California Institute of Technology, Pasadena, CA 91125, United States.
J Inorg Biochem. 2018 Aug;185:86-102. doi: 10.1016/j.jinorgbio.2018.04.021. Epub 2018 May 2.
We extend our study of the structural stability of helical and nonhelical regions in chain A of human intelectin-1 to include a second human intelectin (4WMY) and the frog protein "Xenopus embryonic epidermal lectin" (XEEL). These unique lectins have been shown to recognize carbohydrate residues found exclusively in microbes, thus they could potentially be developed into novel microbe detection and sequestration tools. We believe that by studying the structural stability of these proteins we can provide insights on their biological role and activities. Using a geometrical model introduced previously, we perform computational analyses of protein crystal structures that quantify the resiliency of the native state to steric perturbations. Based on these analyses, we conclude that differences in the resiliency of the human and frog proteins can be attributed primarily to differences in non-helical regions and to residues near Ca ions. Since these differences are particularly pronounced in the vicinity of the ligand binding site, they provide an explanation for the finding that human intelectin-1 has a higher affinity for a ligand than XEEL. We also present data on conserved and position-equivalent pairs of residues in 4WMY and XEEL. We identify residue pairs as well as regions in which the influence of neighboring residues is nearly uniform as the parent protein denatures. Since the structural signatures are conserved, this identification provides a basis for understanding why both proteins exhibit trimeric structures despite poor sequence conservation at the interface.
我们将人类凝集素-1 链 A 中螺旋区和非螺旋区结构稳定性的研究扩展到了另一种人类凝集素（4WMY）和青蛙蛋白“非洲爪蟾胚胎表皮凝集素”（XEEL）。这些独特的凝集素已被证明可以识别仅存在于微生物中的碳水化合物残基，因此它们有可能被开发成新型的微生物检测和隔离工具。我们相信，通过研究这些蛋白质的结构稳定性，我们可以深入了解它们的生物学功能和活性。我们使用之前引入的几何模型，对蛋白质晶体结构进行计算分析，这些分析量化了天然状态对空间干扰的弹性。基于这些分析，我们得出结论，人与青蛙蛋白的弹性差异主要归因于非螺旋区和 Ca 离子附近的残基差异。由于这些差异在配体结合位点附近尤为明显，因此可以解释为什么人类凝集素-1 与配体的亲和力比 XEEL 高。我们还提供了 4WMY 和 XEEL 中保守和位置等价的残基对的数据。我们确定了残基对以及在蛋白质变性时邻近残基的影响几乎均匀的区域。由于结构特征是保守的，这种识别为理解为什么尽管在界面处序列保守性较差，但两种蛋白质都表现出三聚体结构提供了基础。
