Structural basis for synaptic adhesion mediated by neuroligin-neurexin interactions
Structural basis for synaptic adhesion mediated by neuroligin-neurexin interactions
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DOI：
10.1038/nsmb1350
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发表时间：
2008-01-01
影响因子：
16.8
通讯作者：
He, Xiaolin
中科院分区：
文献类型：
--
作者：
Chen, Xiaoyan;Liu, Heli;He, Xiaolin
异质突触粘附分子神经素和神经毒素对于通过调节突触的形成和成熟来建立和维持神经元回路至关重要。神经素素系蛋白的粘附是Ca2+依赖性的，并且受替代剪接的调节。我们报告了小鼠神经素1（NL1）胆碱酯酶样结构域与小鼠Neurexin-1β（NX1β）LNS（laminin，Neurexinin，Neurexin和性激素 - 性激素结合球蛋白样）域之间的2.4埃琴的结构。该结构揭示了由亲水性，Ca2+介导的和溶剂供应的界面介导的微妙神经素维菌素组装，使其能够通过替代剪接和其他调节因素进行调节。热力学数据支持一种机制，其中NL1的剪接位点B通过调节NL1-NX1β界面边缘的盐桥来起作用。与自闭症有关的映射神经素突变表明，大多数此类突变在结构上是稳定的，支持缺乏神经素蛋白的生物合成和加工作为这种脑疾病的共同原因。
The heterophilic synaptic adhesion molecules neuroligins and neurexins are essential for establishing and maintaining neuronal circuits by modulating the formation and maturation of synapses. The neuroligin-neurexin adhesion is Ca2+-dependent and regulated by alternative splicing. We report a structure of the complex at a resolution of 2.4 angstrom between the mouse neuroligin-1 (NL1) cholinesterase-like domain and the mouse neurexin-1 beta (NX1 beta) LNS (laminin, neurexin and sex hormone-binding globulin-like) domain. The structure revealed a delicate neuroligin-neurexin assembly mediated by a hydrophilic, Ca2+-mediated and solvent-supplemented interface, rendering it capable of being modulated by alternative splicing and other regulatory factors. Thermodynamic data supported a mechanism wherein splicing site B of NL1 acts by modulating a salt bridge at the edge of the NL1-NX1 beta interface. Mapping neuroligin mutations implicated in autism indicated that most such mutations are structurally destabilizing, supporting deficient neuroligin biosynthesis and processing as a common cause for this brain disorder.