Hsueh Y P, Kim E, Sheng M
Howard Hughes Medical Institute and Department of Neurobiology, Massachusetts General Hospital and Harvard Medical School, Boston 02214, USA.
Neuron. 1997 May;18(5):803-14. doi: 10.1016/s0896-6273(00)80319-0.
The PSD-95/SAP90 family of PDZ-containing proteins is directly involved in the clustering of specific ion channels at synapses. We report that channel clustering depends on a conserved N-terminal domain of PSD-95 that mediates multimerization and disulfide linkage of PSD-95 protomers. This N-terminal multimerization domain confers channel clustering activity on a single PDZ domain. Thus, channel clustering depends on aggregation of PDZ domains achieved by head-to-head multimerization of PSD-95, rather than by concatenation of PDZ domains in PSD-95 monomers. This mechanism predicts that PSD-95 can organize heterogeneous membrane protein clusters via differential binding specificities of its three PDZ domains. PSD-95 and its relative chapsyn-110 exist as disulfide-linked complexes in rat brain, consistent with head-to-head multimerization of these proteins in vivo.
含PDZ结构域的PSD-95/SAP90蛋白家族直接参与特定离子通道在突触处的聚集。我们报告称，通道聚集取决于PSD-95保守的N端结构域，该结构域介导PSD-95原聚体的多聚化和二硫键连接。这个N端多聚化结构域赋予单个PDZ结构域通道聚集活性。因此，通道聚集取决于通过PSD-95的头对头多聚化实现的PDZ结构域聚集，而不是通过PSD-95单体中PDZ结构域的串联。这一机制预测，PSD-95可通过其三个PDZ结构域的不同结合特异性来组织异质膜蛋白簇。在大鼠脑中，PSD-95及其相关蛋白chapsyn-110以二硫键连接的复合物形式存在，这与这些蛋白在体内的头对头多聚化一致。
