Solution structure of GOPC PDZ domain and its interaction with the C-terminal motif of neuroligin
Solution structure of GOPC PDZ domain and its interaction with the C-terminal motif of neuroligin
复制标题
GOPC PDZ结构域的溶液结构及其与neuroligin C端基序的相互作用
DOI：
10.1110/ps.062087506
复制
发表时间：
2006-09-01
期刊：
影响因子：
8
通讯作者：
Shi, Yunyu
中科院分区：
文献类型：
--
作者：
Li, Xiang;Zhang, Jiahai;Shi, Yunyu
GOPC （Golgi-associated PDZ和coil -coil motif-containing protein）是一种与高尔基体相关的PDZ结构域蛋白，在分泌和内吞途径的囊泡运输中起重要作用。GOPC通过其PDZ结构域与许多其他蛋白质相互作用，如Wnt受体frizzled8和神经素。神经素是一种突触后的神经细胞粘附分子，它与突触前分子神经素结合形成异型细胞间连接。本文报道了GOPC PDZ结构域的核磁共振溶液结构。我们的结果表明，它是一个典型的I类PDZ结构域，包含两个α -螺旋和六个β -链。利用化学位移微扰实验，我们进一步研究了GOPC PDZ结构域与神经素c端基序的结合特性。结果表明，相互作用的系综属于低亲和力的快速交换。利用分子动力学模拟方法构建了GOPC PDZ结构域/神经素c端肽复合物的三维模型。我们的发现为GOPC PDZ结构域与Nlg c端肽的特异性相互作用提供了见解，也为Nlg与其他含有PDZ结构域的蛋白质相互作用的可能结合模式提供了一般的见解。
GOPC (Golgi-associated PDZ and coiled-coil motif-containing protein) represents a PDZ domain-containing protein associated with the Golgi apparatus, which plays important roles in vesicular trafficking in secretory and endocytic pathways. GOPC interacts with many other proteins, such as the Wnt receptors Frizzled 8 and neuroligin via its PDZ domain. Neuroligin is a neural cell-adhesion molecule of the post-synapse, which binds to the presynapse molecule neurexin to form a heterotypic intercellular junction. Here we report the solution structure of the GOPC PDZ domain by NMR. Our results show that it is a canonical class I PDZ domain, which contains two alpha-helices and six beta-strands. Using chemical shift perturbation experiments, we further studied the binding properties of the GOPC PDZ domain with the C-terminal motif of neuroligin. The observations showed that the ensemble of the interaction belongs to fast exchange with low affinity. The 3D model of the GOPC PDZ domain/ neuroligin C-terminal peptide complex was constructed with the aid of the molecular dynamics simulation method. Our discoveries provide insight into the specific interaction of the GOPC PDZ domain with the C-terminal peptide of Nlg and also provide a general insight about the possible binding mode of the interaction of Nlg with other PDZ domain-containing proteins.