Snyder Greg A, Colonna Marco, Sun Peter D
Laboratory of Immunogenetics, Structural Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Twinbrook II, 12441 Parklawn Drive, Rockville, MD 20852, USA.
J Mol Biol. 2005 Apr 15;347(5):979-89. doi: 10.1016/j.jmb.2005.01.063.
The dendritic cell-specific ICAM-3 non-integrin (DC-SIGN) and its close relative DC-SIGNR recognize various glycoproteins, both pathogenic and cellular, through the receptor lectin domain-mediated carbohydrate recognition. While the carbohydrate-recognition domains (CRD) exist as monomers and bind individual carbohydrates with low affinity and are permissive in nature, the full-length receptors form tetramers through their repeat domain and recognize specific ligands with high affinity. To understand the tetramer-based ligand binding avidity, we determined the crystal structure of DC-SIGNR with its last repeat region. Compared to the carbohydrate-bound CRD structure, the structure revealed conformational changes in the calcium and carbohydrate coordination loops of CRD, an additional disulfide bond between the N and the C termini of the CRD, and a helical conformation for the last repeat. On the basis of the current crystal structure and other published structures with sequence homology to the repeat domain, we generated a tetramer model for DC-SIGN/R using homology modeling and propose a ligand-recognition index to identify potential receptor ligands.
树突状细胞特异性细胞间黏附分子3非整合素（DC-SIGN）及其近亲DC-SIGNR通过受体凝集素结构域介导的碳水化合物识别作用，识别各种糖蛋白，包括致病性糖蛋白和细胞源性糖蛋白。虽然碳水化合物识别结构域（CRD）以单体形式存在，与单个碳水化合物的结合亲和力较低且具有宽松性，但全长受体通过其重复结构域形成四聚体，并以高亲和力识别特定配体。为了理解基于四聚体的配体结合亲和力，我们确定了带有最后一个重复区域的DC-SIGNR的晶体结构。与结合碳水化合物的CRD结构相比，该结构揭示了CRD的钙和碳水化合物配位环的构象变化、CRD的N端和C端之间额外的二硫键以及最后一个重复区域的螺旋构象。基于当前的晶体结构以及其他已发表的与重复结构域具有序列同源性的结构，我们利用同源建模生成了DC-SIGN/R的四聚体模型，并提出了一种配体识别指数来鉴定潜在的受体配体。
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