Attrill Helen, Imamura Akihiro, Sharma Ritu S, Kiso Makoto, Crocker Paul R, van Aalten Daan M F
Division of Biological Chemistry and Molecular Microbiology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom.
J Biol Chem. 2006 Oct 27;281(43):32774-83. doi: 10.1074/jbc.M601714200. Epub 2006 Aug 8.
The siglecs are a group of mammalian sialic acid binding receptors expressed predominantly in the immune system. The CD33-related siglecs show complex recognition patterns for sialylated glycans. Siglec-7 shows a preference for alpha(2,8)-disialylated ligands and provides a structural template for studying the key interactions that drive this selectivity. We have co-crystallized Siglec-7 with a synthetic oligosaccharide corresponding to the alpha(2,8)-disialylated ganglioside GT1b. The crystal structure of the complex offers a first glimpse into how this important family of lectins binds the structurally diverse gangliosides. The structure reveals that the C-C' loop, a region implicated in previous studies as driving siglec specificity, undergoes a dramatic conformational shift, allowing it to interact with the underlying neutral glycan core of the ganglioside. The structural data in combination with mutagenesis studies show that binding of the ganglioside is driven by extensive hydrophobic contacts together with key polar interactions and that the binding site structure is complementary to preferred solution conformations of GT1b.
唾液酸结合免疫球蛋白样凝集素（Siglec）是一类主要在免疫系统中表达的哺乳动物唾液酸结合受体。与CD33相关的Siglec对唾液酸化聚糖表现出复杂的识别模式。Siglec-7对α(2,8)-二唾液酸化配体具有偏好性，并为研究驱动这种选择性的关键相互作用提供了结构模板。我们已将Siglec-7与对应于α(2,8)-二唾液酸化神经节苷脂GT1b的合成寡糖共结晶。该复合物的晶体结构首次揭示了这个重要的凝集素家族如何结合结构多样的神经节苷脂。结构显示，C-C'环（先前研究表明该区域驱动Siglec的特异性）发生了显著的构象变化，使其能够与神经节苷脂潜在的中性聚糖核心相互作用。结构数据与诱变研究相结合表明，神经节苷脂的结合是由广泛的疏水接触以及关键的极性相互作用驱动的，并且结合位点结构与GT1b的优选溶液构象互补。
