Multivalent Binding of Carbohydrates by the Human α-Defensin, HD5
Multivalent Binding of Carbohydrates by the Human α-Defensin, HD5
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DOI：
10.4049/jimmunol.0900244
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发表时间：
2009-07-01
影响因子：
4.4
通讯作者：
Lu, Wuyuan
中科院分区：
文献类型：
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作者：
Lehrer, Robert I.;Jung, Grace;Lu, Wuyuan
六种人α-防御素中的四种（人嗜中性粒细胞肽1-3和人α-防御素5; HD 5）具有凝集素样结合糖基化蛋白的能力。使用HD 5作为模型，我们应用表面等离子体共振技术来深入了解这一属性。HD 5结合天然糖蛋白>基于BSA的新糖蛋白>非糖基化BSA >>游离糖。HD 5对与BSA共价结合的单糖的亲和力比其对溶液中相同糖的亲和力大几个数量级。HD 5对蛋白质结合碳水化合物的亲和力来自多价相互作用，这也可能涉及蛋白质的非碳水化合物残基。HD 5显示浓度依赖性的自缔合，开始在亚微摩尔浓度，并进行二聚体和四聚体形成在浓度低于5 μ M。HD 5的（R9 A，R28 A）和（RDA，R32 A）类似物显示出极大降低的自缔合以及与BSA和BSA固定的糖的最小结合。从这个和其他证据，我们得出结论，广泛的结合HD 5（新）糖蛋白的结果从多价非特异性相互作用的个别HD 5分子与碳水化合物和非碳水化合物部分的目标分子和主要的结合事件被放大和增强随后的原位组装和寡聚化的HD 5。自缔合和多价结合可能在HD 5保护免受由病毒和其他感染因子引起的感染的能力中发挥不可或缺的作用。免疫学杂志，2009，183：480-490。
Four of the six human alpha-defensins (human neutrophil peptides 1-3 and human a-defensin 5; HD5) have a lectin-like ability to bind glycosylated proteins. Using HD5 as a model, we applied surface plasmon resonance techniques to gain insights into this property. HD5 bound natural glycoproteins > neoglycoproteins based on BSA > nonglycosylated BSA >> free sugars. The affinity of HD5 for simple sugars covalently bound to BSA was orders of magnitude greater than its affinity for the same sugars in solution. The affinity of HD5 for protein-bound carbohydrates resulted from multivalent interactions which may also involve noncarbohydrate residues of the proteins. HD5 showed concentration-dependent self-association that began at submicromolar concentrations and proceeded to dimer and tetramer formation at concentrations below 5 mu M. The (R9A, R28A) and (RDA, R32A) analogs of HD5 showed greatly reduced self-association as well as minimal binding to BSA and to BSA-affixed sugars. From this and other evidence, we conclude that the extensive binding of HD5 to (neo)glycoproteins results from multivalent nonspecific interactions of individual HD5 molecules with carbohydrate and noncarbohydrate moieties of the target molecule and that the primary binding events are magnified and enhanced by subsequent in situ assembly and oligomerization of HD5. Self-association and multivalent binding may play integral roles in the ability of HD5 to protect against infections caused by viruses and other infectious agents. The Journal of Immunology, 2009, 183: 480-490.