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人半乳糖凝集素-7对基于多价半乳糖的树枝状大分子识别的结构基础。

Structural basis of multivalent galactose-based dendrimer recognition by human galectin-7.

作者信息

Ramaswamy Sneha, Sleiman Mazen H, Masuyer Geoffrey, Arbez-Gindre Cécile, Micha-Screttas Maria, Calogeropoulou Theodora, Steele Barry R, Acharya K Ravi

机构信息

Department of Biology and Biochemistry, University of Bath, UK.

出版信息

FEBS J. 2015 Jan;282(2):372-87. doi: 10.1111/febs.13140. Epub 2014 Nov 24.

DOI:10.1111/febs.13140
PMID:25367374
Abstract

Galectins are evolutionarily conserved and ubiquitously present animal lectins with a high affinity for β-galactose-containing oligosaccharides. To date, 15 mammalian galectins have been identified. Their involvement in cell-cell and cell-matrix interactions has highlighted their importance in signal transduction and other intracellular processes. Human galectin-7 (hGal-7) is a 15 kDa proto type galectin that forms a dimer in solution and its involvement in the stimulation and development of tumour growth has been reported. Previously, we reported the crystal structure of hGal-7 and its complex with galactose and lactose which provided insight into its molecular recognition and detailed interactions. Here, we present newly obtained high-resolution structural data on carbohydrate-based dendrons in complex with hGal-7. Our crystallographic data reveal how multivalent ligands interact with and form cross-links with these galectin molecules. Understanding how these dendrimeric compounds interact with hGal-7 would help in the design of new tools to investigate the recognition of carbohydrates by lectins.

摘要

半乳糖凝集素是进化上保守且广泛存在的动物凝集素,对含β-半乳糖的寡糖具有高亲和力。迄今为止,已鉴定出15种哺乳动物半乳糖凝集素。它们参与细胞间和细胞与基质的相互作用,凸显了它们在信号转导和其他细胞内过程中的重要性。人半乳糖凝集素-7(hGal-7)是一种15 kDa的原型半乳糖凝集素,在溶液中形成二聚体,并且已有报道其参与肿瘤生长的刺激和发展。此前,我们报道了hGal-7及其与半乳糖和乳糖复合物的晶体结构,这为其分子识别和详细相互作用提供了见解。在此,我们展示了新获得的与hGal-7复合的基于碳水化合物的树枝状分子的高分辨率结构数据。我们的晶体学数据揭示了多价配体如何与这些半乳糖凝集素分子相互作用并形成交联。了解这些树枝状化合物如何与hGal-7相互作用将有助于设计新工具来研究凝集素对碳水化合物的识别。

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