Structural analysis of the synaptic protein neuroligin and its β-neurexin complex:: Determinants for folding and cell adhesion
Structural analysis of the synaptic protein neuroligin and its β-neurexin complex:: Determinants for folding and cell adhesion
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DOI：
10.1016/j.neuron.2007.11.013
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发表时间：
2007-12-20
期刊：
影响因子：
16.2
通讯作者：
Marchot, Pascale
中科院分区：
文献类型：
--
作者：
Fabrichny, Igor P.;Leone, Philippe;Marchot, Pascale
神经连接蛋白是突触后细胞黏附蛋白，其与突触前神经尿蛋白的关系参与突触的形成。神经连接蛋白和神经毒素基因的突变似乎与自闭症和智力低下有关。神经连接蛋白的晶体结构揭示了其催化活性同系物中没有的特征，例如形成功能性神经连接蛋白二聚体的完全疏水界面；残留活性中心周围表面环的构象；对折叠和加工至关重要的决定簇的位置；以及没有大分子偶极和存在与neuresin结合的电负性亲水性表面。该复合体的结构揭示了结合的神经连接蛋白的精确定位，尽管分辨率有限，但仍提供了涉及跨突触神经连接蛋白结合的钙离子依赖的相互作用网络的大量信息。这些结构举例说明了α/β-水解酶折叠如何在表面形貌中变化以赋予粘附性，并提供用于分析与自闭症相关的异常处理或识别事件的模板。
The neuroligins are postsynaptic cell adhesion proteins whose associations with presynaptic neurexins participate in synaptogenesis. Mutations in the neuroligin and neurexin genes appear to be associated with autism and mental retardation. The crystal structure of a neuroligin reveals features not found in its catalytically active relatives, such as the fully hydrophobic interface forming the functional neuroligin dimer; the conformations of surface loops surrounding the vestigial active center; the location of determinants that are critical for folding and processing; and the absence of a macromolecular dipole and presence of an electronegative, hydrophilic surface for neurexin binding. The structure of a beta-neurexin-neuroligin complex reveals the precise orientation of the bound neurexin and, despite a limited resolution, provides substantial information on the Ca2+- dependent interactions network involved in trans-synaptic neurexin-neuroligin association. These structures exemplify how an alpha/beta-hydrolase fold varies in surface topography to confer adhesion properties and provide templates for analyzing abnormal processing or recognition events associated with autism.