Structural basis for langerin recognition of diverse pathogen and mammalian glycans through a single binding site.
Structural basis for langerin recognition of diverse pathogen and mammalian glycans through a single binding site.
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DOI：
10.1016/j.jmb.2010.11.039
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发表时间：
2011-01-28
影响因子：
5.6
通讯作者：
Weis WI
中科院分区：
文献类型：
--
作者：
Feinberg H;Taylor ME;Razi N;McBride R;Knirel YA;Graham SA;Drickamer K;Weis WI
在抗原呈递给适应性免疫系统的第一步，langerin介导了郎格汉斯细胞对病原体的碳水化合物依赖的摄取。Langerin与数量异常多样的内源性和致病细胞表面碳水化合物结合，包括从细菌脂多糖中提取的含有甘露糖的O-特异性多糖，这里通过探测细菌多糖微阵列确定了这些多糖。人Langerin的糖识别域与一系列低聚糖化合物、B血型抗原和一段β-葡聚糖结合的晶体结构表明，与甘露糖、岩藻糖和葡萄糖残基结合的是具有类似立体化学的邻位羟基的钙配位。低聚甘露糖化合物通过单一的甘露糖残基结合，没有其他甘露糖残基直接与蛋白质接触。没有证据表明存在第二个不依赖于钙离子的结合位点。同样，β-葡聚糖片段Glcβ1-3Glcβ1-3Glc通过单个葡萄糖残基与钙离子位点的相互作用与Langerin结合。血型B型三糖半乳糖α1-3(Fucα1-2)的岩藻糖部分也与钙离子结合，与其他含岩藻糖低聚糖相比，选择性结合到该糖是由于非还原末端半乳糖以及岩藻糖残基的额外有利相互作用。令人惊讶的是，6SO4-Galβ1-4GlcNAc中半乳糖残基的赤道3-OH基团和轴向4-OH基团也与钙离子配位，这是一种迄今未观察到的半乳糖结合方式，在C型碳水化合物识别结构域中具有甘露糖结合位点的特征基序。硫酸盐基团和两个赖氨酸残基之间的盐桥似乎弥补了半乳糖在这个位置的非最佳结合。
Langerin mediates the carbohydrate-dependent uptake of pathogens by Langerhans cells in the first step of antigen presentation to the adaptive immune system. Langerin binds to an unusually diverse number of endogenous and pathogenic cell surface carbohydrates, including mannose-containing O-specific polysaccharides derived from bacterial lipopolysaccharides identified here by probing a microarray of bacterial polysaccharides. Crystal structures of the carbohydrate-recognition domain from human langerin bound to a series of oligomannose compounds, the blood group B antigen, and a fragment of β-glucan reveal binding to mannose, fucose, and glucose residues by Ca2+ coordination of vicinal hydroxyl groups with similar stereochemistry. Oligomannose compounds bind through a single mannose residue, with no other mannose residues contacting the protein directly. There is no evidence for a second Ca2+-independent binding site. Likewise, a β-glucan fragment, Glcβ1–3Glcβ1–3Glc, binds to langerin through the interaction of a single glucose residue with the Ca2+ site. The fucose moiety of the blood group B trisaccharide Galα1–3(Fucα1–2)Gal also binds to the Ca2+ site, and selective binding to this glycan compared to other fucose-containing oligosaccharides results from additional favorable interactions of the nonreducing terminal galactose, as well as of the fucose residue. Surprisingly, the equatorial 3-OH group and the axial 4-OH group of the galactose residue in 6SO4–Galβ1–4GlcNAc also coordinate Ca2+, a heretofore unobserved mode of galactose binding in a C-type carbohydrate-recognition domain bearing the Glu-Pro-Asn signature motif characteristic of mannose binding sites. Salt bridges between the sulfate group and two lysine residues appear to compensate for the nonoptimal binding of galactose at this site.
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影响因子：
3.6
作者：
de Jong MA;Vriend LE;Theelen B;Taylor ME;Fluitsma D;Boekhout T;Geijtenbeek TB
通讯作者：
Geijtenbeek TB
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
56.9
作者：
Feinberg, H;Mitchell, DA;Weis, WI
通讯作者：
Weis, WI
影响因子：
5.5
作者：
de Jong, Marein A. W. P.;de Witte, Lot;Geijtenbeek, Teunis B. H.
通讯作者：
Geijtenbeek, Teunis B. H.
影响因子：
4.8
作者：
Feinberg, Hadar;Castelli, Riccardo;Weis, William I.
通讯作者：
Weis, William I.