Polarity is a fundamental property of most cell types. The Par protein complex is a major driving force in generating asymmetrically localized protein networks and consists of atypical protein kinase C (aPKC), Par3, and Par6. Dysfunction of this complex causes developmental abnormalities and diseases such as cancer. We identified a PDZ domain–binding motif in Par6 that was essential for its interaction with Par3 in vitro and for Par3-mediated membrane localization of Par6 in cultured cells. In fly embryos, we observed that the PDZ domain–binding motif was functionally redundant with the PDZ domain in targeting Par6 to the cortex of epithelial cells. Our structural analyses by x-ray crystallography and NMR spectroscopy showed that both the PDZ1 and PDZ3 domains but not the PDZ2 domain in Par3 engaged in a canonical interaction with the PDZ domain–binding motif in Par6. Par3 thus has the potential to recruit two Par6 proteins simultaneously, which may facilitate the assembly of polarity protein networks through multivalent PDZ domain interactions.

极性是大多数电池类型的基本属性。Par蛋白复合物是产生不对称局部蛋白网络的主要驱动力，由非典型蛋白激酶C（aPKC），Par3和Par6组成。这种复合物的功能障碍会导致发育异常和疾病，例如癌症。我们在Par6中鉴定了一个PDZ结构域结合基序，这是其与Par3在体外相互作用以及在培养细胞中Par6介导的Par6膜定位所必需的。在果蝇胚胎中，我们观察到PDZ结构域结合基序在功能上与PDZ结构域在将Par6靶向上皮细胞皮层时是多余的。我们通过X射线晶体学和NMR谱进行的结构分析表明，Par3中的PDZ1和PDZ3结构域，而不是PDZ2结构域，都与Par6中的PDZ结构域结合基序进行了规范的相互作用。因此，Par3有可能同时募集两个Par6蛋白，这可能有助于通过多价PDZ域相互作用来组装极性蛋白网络。