Department of Structural Biology, Stanford University School of Medicine, Stanford, California 94306, USA.
J Biol Chem. 2010 Apr 23;285(17):13285-93. doi: 10.1074/jbc.M109.086058. Epub 2010 Feb 24.
Langerin, an endocytic receptor of Langerhans cells, binds pathogens such as human immunodeficiency virus by recognition of surface glycoconjugates and mediates their internalization into Birbeck granules. Langerin has an extracellular region consisting of a C-type carbohydrate-recognition domain (CRD) and a neck region that stabilizes formation of trimers. As in many other C-type lectins, oligomerization is required for high affinity binding to glycan ligands and is also likely to be important for determining specificity. To facilitate structural analysis of the human langerin trimer, a truncated form of the extracellular region, consisting of part of the neck and the CRD, has been characterized. Like the full-length protein, truncated langerin exists as a stable trimer in solution. Glycan array screening with the trimeric fragment shows that high mannose oligosaccharides are the best ligands for langerin. Structural analysis of the trimeric fragment of langerin confirms that the neck region forms a coiled-coil of alpha-helices. Multiple interactions between the neck region and the CRDs make the trimer a rigid unit with the three CRDs in fixed positions and the primary sugar-binding sites separated by a distance of 42 A. The fixed orientation of the sugar-binding sites in the trimer is likely to place constraints on the ligands that can be bound by langerin.
朗格汉斯细胞的内吞受体朗格素通过识别表面糖缀合物来结合病原体，如人类免疫缺陷病毒，并介导它们被内吞到贝克颗粒中。朗格素的细胞外区域由 C 型碳水化合物识别结构域（CRD）和稳定三聚体形成的颈部区域组成。与许多其他 C 型凝集素一样，寡聚化是与糖配体高亲和力结合所必需的，对于确定特异性也可能很重要。为了促进人类朗格素三聚体的结构分析，已经对包含颈部和 CRD 部分的细胞外区域的截断形式进行了表征。与全长蛋白一样，截短的朗格素以稳定的三聚体形式存在于溶液中。用三聚体片段进行糖阵列筛选表明，高甘露糖寡糖是朗格素的最佳配体。对朗格素三聚体片段的结构分析证实，颈部区域形成了一个α-螺旋的卷曲螺旋。颈部区域和 CRD 之间的多种相互作用使三聚体成为一个刚性单元，三个 CRD 处于固定位置，主要的糖结合位点之间的距离为 42 A。三聚体中糖结合位点的固定取向可能会限制朗格素可以结合的配体。
