Structural basis for tandem L27 domain-mediated polymerization
Structural basis for tandem L27 domain-mediated polymerization
复制标题
串联 L27 结构域介导的聚合的结构基础
DOI：
10.1096/fj.10-163857
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发表时间：
2010-12-01
期刊：
影响因子：
4.8
通讯作者：
Shen, Yuequan
中科院分区：
文献类型：
--
作者：
Yang, Xue;Xie, Xingqiao;Shen, Yuequan
上皮细胞极性的建立需要多蛋白复合物的组装，并且在上皮形态发生过程中至关重要。三种支架蛋白 Dlg1、MPP7 和 Mals3 可以组装形成复合物，通过其 L27 结构域在上皮组织中建立和维持顶端基底极性方面发挥作用。在这里，我们结合顺磁弛豫增强测量报告了源自人类三联复合物 Dlg1-MPP7-Mals3 的 4-L27 结构域复合物的晶体结构。异源三聚体由 2 对异源二聚体 L27 结构域组成。由于 MPP7 的 N 端和 C 端串联 L27 结构域之间存在巨大差异，这 2 个二聚体是不对称的。结构分析结合生化实验进一步揭示MPP7 C端L27结构域的环αA-αB和螺旋αB在组装整个三联复合物中发挥着关键作用，表明L27介导的协同串联组装事件。-Yang, X., Xie, X., Chen, L., Zhou, H., Wang, Z., 赵，W.，田，R.，张，R.，田，C.，龙，J.，沉，Y.串联L27域介导的聚合的结构基础。 FASEB J. 24, 4806-4815 (2010)。 www.fasebj.org
The establishment of epithelial cell polarity requires the assembly of multiprotein complexes and is crucial during epithelial morphogenesis. Three scaffolding proteins, Dlg1, MPP7, and Mals3, can be assembled to form a complex that functions in the establishment and maintenance of apicobasal polarity in epithelial tissues through their L27 domains. Here we report the crystal structure of a 4-L27-domain complex derived from the human tripartite complex Dlg1-MPP7-Mals3 in combination with paramagnetic relaxation enhancement measurements. The heterotrimer consists of 2 pairs of heterodimeric L27 domains. These 2 dimers are asymmetric due to the large difference between the N- and C-terminal tandem L27 domain of MPP7. Structural analysis combined with biochemical experiments further reveals that the loop alpha A-alpha B and helix alpha B of the C-terminal L27 domain of MPP7 play a critical role in assembling the entire tripartite complex, suggesting a synergistic tandem L27-mediated assembling event.-Yang, X., Xie, X., Chen, L., Zhou, H., Wang, Z., Zhao, W., Tian, R., Zhang, R., Tian, C., Long, J., Shen, Y. Structural basis for tandem L27 domain- mediated polymerization. FASEB J. 24, 4806-4815 (2010). www.fasebj.org