Garlatti Virginie, Belloy Nicolas, Martin Lydie, Lacroix Monique, Matsushita Misao, Endo Yuichi, Fujita Teizo, Fontecilla-Camps Juan Carlos, Arlaud Gérard J, Thielens Nicole M, Gaboriaud Christine
Laboratoire de Cristallographie et Cristallogénèse des Protéines, Grenoble, France.
EMBO J. 2007 Jan 24;26(2):623-33. doi: 10.1038/sj.emboj.7601500. Epub 2007 Jan 11.
Innate immunity relies critically upon the ability of a few pattern recognition molecules to sense molecular markers on pathogens, but little is known about these interactions at the atomic level. Human L- and H-ficolins are soluble oligomeric defence proteins with lectin-like activity, assembled from collagen fibers prolonged by fibrinogen-like recognition domains. The X-ray structures of their trimeric recognition domains, alone and in complex with various ligands, have been solved to resolutions up to 1.95 and 1.7 A, respectively. Both domains have three-lobed structures with clefts separating the distal parts of the protomers. Ca(2+) ions are found at sites homologous to those described for tachylectin 5A (TL5A), an invertebrate lectin. Outer binding sites (S1) homologous to the GlcNAc-binding pocket of TL5A are present in the ficolins but show different structures and specificities. In L-ficolin, three additional binding sites (S2-S4) surround the cleft. Together, they define an unpredicted continuous recognition surface able to sense various acetylated and neutral carbohydrate markers in the context of extended polysaccharides such as 1,3-beta-D-glucan, as found on microbial or apoptotic surfaces.
天然免疫关键依赖于少数模式识别分子感知病原体上分子标记的能力，但在原子水平上对这些相互作用却知之甚少。人L-和H-纤维胶凝蛋白是具有凝集素样活性的可溶性寡聚防御蛋白，由通过纤维蛋白原样识别结构域延长的胶原纤维组装而成。它们三聚体识别结构域单独以及与各种配体结合的X射线结构分别已解析到高达1.95 Å和1.7 Å的分辨率。两个结构域均具有三叶结构，裂隙将原体的远端部分隔开。在与无脊椎动物凝集素速激肽凝集素5A（TL5A）所描述的位点同源的位点发现了Ca(2+)离子。纤维胶凝蛋白中存在与TL5A的GlcNAc结合口袋同源的外部结合位点（S1），但显示出不同的结构和特异性。在L-纤维胶凝蛋白中，另外三个结合位点（S2-S4）围绕裂隙。它们共同定义了一个意想不到的连续识别表面，能够在扩展多糖（如在微生物或凋亡表面发现的1,3-β-D-葡聚糖）的背景下感知各种乙酰化和中性碳水化合物标记。
