Crystal structure of the v domain of human nectin-like molecule-1/Syncam3/Tsll1/Igsf4b, a neural tissue-specific immunoglobulin-like cell-cell adhesion molecule
Crystal structure of the v domain of human nectin-like molecule-1/Syncam3/Tsll1/Igsf4b, a neural tissue-specific immunoglobulin-like cell-cell adhesion molecule
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DOI：
10.1074/jbc.m513459200
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发表时间：
2006-04-14
影响因子：
4.8
通讯作者：
Rao, ZH
中科院分区：
文献类型：
--
作者：
Dong, XH;Xu, F;Rao, ZH
Nectin是钙离子非依赖性免疫球蛋白（IG）超家族蛋白，参与上皮和内皮连接的组织化。Nectin在胞外区具有三个Ig样结构域，第一个结构域在细胞-细胞粘附中是必需的，并且在与几种病毒的包膜糖蛋白D的相互作用中起核心作用。已经鉴定了五种与Nectins具有相似结构域结构的Nectin样分子（Necl-1至Necl-5）。Necl-1在神经组织中特异性表达，具有Ca 2+非依赖性嗜同性和嗜异性细胞-细胞粘附活性，并且在突触、轴突束和有髓轴突的形成中起重要作用。在这里，我们报告了其N-末端Ig样V结构域在2.4埃的第一个晶体结构，提供了深入了解Necl-1介导的跨细胞识别。该蛋白质结晶为二聚体，并通过尺寸排阻色谱和化学交联实验证实了二聚体形式，表明该V结构域足以进行亲同性相互作用。诱变工作证明Phe（82）是Necl-1粘附活性的关键残基。根据Necl-1的结构和以往的研究，提出了一个Necl-1在突触上的嗜同性粘附模型。
Nectins are Ca2+-independent immunoglobulin (Ig) superfamily proteins that participate in the organization of epithelial and endothelial junctions. Nectins have three Ig-like domains in the extracellular region, and the first one is essential in cell-cell adhesion and plays a central role in the interaction with the envelope glycoprotein D of several viruses. Five Nectin-like molecules (Necl-1 through -5) with similar domain structures to those of Nectins have been identified. Necl-1 is specifically expressed in neural tissue, has Ca2+-independent homophilic and heterophilic cell-cell adhesion activity, and plays an important role in the formation of synapses, axon bundles, and myelinated axons. Here we report the first crystal structure of its N-terminal Ig-like V domain at 2.4 angstrom, providing insight into trans-cellular recognition mediated by Necl-1. The protein crystallized as a dimer, and the dimeric form was confirmed by size-exclusion chromatography and chemical cross-linking experiments, indicating this V domain is sufficient for homophilic interaction. Mutagenesis work demonstrated that Phe(82) is a key residue for the adhesion activity of Necl-1. A model for homophilic adhesion of Necl-1 at synapses is proposed based on its structure and previous studies.