Crystal Structure of a Complex of Surfactant Protein D (SP-D) and Haemophilus influenzae Lipopolysaccharide Reveals Shielding of Core Structures in SP-D-Resistant Strains
Crystal Structure of a Complex of Surfactant Protein D (SP-D) and Haemophilus influenzae Lipopolysaccharide Reveals Shielding of Core Structures in SP-D-Resistant Strains
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DOI：
10.1128/iai.01239-15
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发表时间：
2016-05-01
影响因子：
3.1
通讯作者：
Shrive, Annette K.
中科院分区：
文献类型：
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作者：
Clark, Howard W.;Mackay, Rose-Marie;Shrive, Annette K.
肺表面活性蛋白D（SP-D）的碳水化合物识别结构域（CRD）识别肺部病原体表面的糖模式并促进吞噬作用。使用流感嗜血杆菌埃根菌株表达良好的特点脂多糖（LPS）表面结构的各种复杂程度，我们表明，细菌识别和结合SP-D是负相关的LPS链的范围和复杂性。与脱脂埃根4A LPS复合的生物活性重组三聚体SP-D CRD的晶体结构表明，SP-D的有效LPS识别需要利用SP-D结合口袋中的三个主要配体结合决定簇的多重结合相互作用，其中内核庚糖的Ca依赖性结合伴随脱水-Kdo的相互作用（4，7-脱水-3-脱氧-D-甘露-辛-2-酮糖酸）与Arg 343和Asp 325。结合酶联免疫吸附试验（ELISA）和荧光激活细胞分选仪（FACS）结合分析，我们的研究结果表明，以前被认为是collectins的目标的扩展LPS结构在屏蔽LPS核心中更脆弱的位点方面非常重要，揭示了一种机制，通过这种机制，具有复杂LPS扩展的病原体有效地逃避了一线粘膜先天免疫防御。该结构还首次揭示了无水KDO的主要形式。
The carbohydrate recognition domains (CRDs) of lung collectin surfactant protein D (SP-D) recognize sugar patterns on the surface of lung pathogens and promote phagocytosis. Using Haemophilus influenzae Eagan strains expressing well-characterized lipopolysaccharide (LPS) surface structures of various levels of complexity, we show that bacterial recognition and binding by SP-D is inversely related to LPS chain extent and complexity. The crystal structure of a biologically active recombinant trimeric SP-D CRD complexed with a delipidated Eagan 4A LPS suggests that efficient LPS recognition by SP-D requires multiple binding interactions utilizing the three major ligand-binding determinants in the SP-D binding pocket, with Ca-dependent binding of inner-core heptose accompanied by interaction of anhydro-Kdo (4,7-anhydro-3-deoxy-D-manno-oct-2-ulosonic acid) with Arg343 and Asp325. Combined with enzyme-linked immunosorbent assays (ELISAs) and fluorescence-activated cell sorter (FACS) binding analyses, our results show that extended LPS structures previously thought to be targets for collectins are important in shielding the more vulnerable sites in the LPS core, revealing a mechanism by which pathogens with complex LPS extensions efficiently evade a first-line mucosal innate immune defense. The structure also reveals for the first time the dominant form of anhydro-Kdo.