Crystal structure of the galectin-9 N-terminal carbohydrate recognition domain from Mus musculus reveals the basic mechanism of carbohydrate recognition
Crystal structure of the galectin-9 N-terminal carbohydrate recognition domain from Mus musculus reveals the basic mechanism of carbohydrate recognition
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DOI：
10.1074/jbc.m606648200
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发表时间：
2006-11-24
影响因子：
4.8
通讯作者：
Kato, Ryuichi
中科院分区：
文献类型：
--
作者：
Nagae, Masamichi;Nishi, Nozomu;Kato, Ryuichi
Galectins是一个与β-半乳糖苷结合的动物凝集素家族，具有保守的碳水化合物识别结构域(CRD)。它们对小的β-半乳糖苷有很高的亲和力，但对复杂的糖偶联物的结合特异性在家族内差别很大。配体的识别对于它们的正常功能是必不可少的，几个Galectins的结构表明了它们与碳水化合物结合的机制。Galectin-9有两个串联的短链CRD，我们报道了小鼠Galectin-9N端CRD(NCRD)在没有和存在四种配体络合物的情况下的晶体结构。所有结构形成相同的二聚体，这与Galectin-1和-2的典型的2倍对称二聚体非常不同。Galectin-9 NCRD中的β-半乳糖苷识别机制在其他Galectins中是高度保守的。在载脂蛋白结构中，水分子模拟了配体的氢键网络。Galectin-9 NCRD可与N-乙酰乳糖胺(Galβ1-4GlcNAc)和T抗原(Galβ1-3GalNAc)结合，并与Arg-结合。此外，N-乙酰乳糖胺二聚体(Galβ1-4GlcNAcβ1-3Gal Beta 1-4GlcNAc)复合体的结构显示了Galectin-9独特的结合模式。表面等离子体共振分析表明，Galectin-9 NCRD不仅在晶体中形成了均亲二聚体，而且在溶液中也形成了均亲二聚体。
The galectins are a family of beta-galactoside-binding animal lectins with a conserved carbohydrate recognition domain (CRD). They have a high affinity for small beta-galactosides, but binding specificity for complex glycoconjugates varies considerably within the family. The ligand recognition is essential for their proper function, and the structures of several galectins have suggested their mechanism of carbohydrate binding. Galectin-9 has two tandem CRDs with a short linker, and we report the crystal structures of mouse galectin-9N-terminal CRD (NCRD) in the absence and the presence of four ligand complexes. All structures form the same dimer, which is quite different from the canonical 2-fold symmetric dimer seen for galectin-1 and -2. The beta-galactoside recognition mechanism in the galectin-9 NCRD is highly conserved among other galectins. In the apo form structure, water molecules mimic the ligand hydrogen-bond network. The galectin-9 NCRD can bind both N-acetyllactosamine (Gal beta 1-4GlcNAc) and T-antigen (Gal beta 1-3GalNAc) with the proper location of Arg-64. Moreover, the structure of the N-acetyllactosamine dimer (Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4GlcNAc) complex shows a unique binding mode of galectin-9. Finally, surface plasmon resonance assay showed that the galectin-9 NCRD forms a homophilic dimer not only in the crystal but also in solution.