L27, a novel heterodimerization domain in receptor targeting proteins Lin-2 and Lin-7
L27, a novel heterodimerization domain in receptor targeting proteins Lin-2 and Lin-7
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DOI：
10.1016/s0968-0004(00)01599-1
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发表时间：
2000-07-01
影响因子：
13.8
通讯作者：
Margolis, B
中科院分区：
文献类型：
--
作者：
Doerks, T;Bork, P;Margolis, B
膜相关鸟苷酸激酶 (MAGUK) 正在成为细胞表面蛋白组织及其与细胞骨架相互作用的关键 1。它们参与细胞连接组织和肿瘤抑制。最近的研究表明，秀丽隐杆线虫 MAGUK 蛋白 Lin-2 对于将线虫生长因子受体 Let-23 正确靶向到上皮细胞 2 的基底外侧表面至关重要。Lin-7 和 Lin-10 也是在线虫中该受体的基底外侧靶向所必需的，并与 Lin-2 形成复合物（参考文献 3）。哺乳动物 Lin-7（或 Veli）4 还被发现与其他几种较小的 Lin-2 相关 MAGUK 蛋白相关，包括 Dlg2、Dlg3、Pals1 和 Pals2（参考文献 5）。Lin-2 和 Lin-7 相关蛋白含有 PDZ 结构域（即 PSD-95、dlg 和 ZO-1/2 中存在的结构域），该结构域不参与与其他 Lin 蛋白 3、4 的复合物形成。 PSI-BLAST 搜索Dlg2 的 PDZ 结构域 7 之前的 N 端区域的 6 检索了 MAGUKS Lin-2 家族的所有成员。这些蛋白质的 DOTPLOT 8 二维视觉比较分析表明存在内部重复，MACAW 比对分析 9 证实了这一点（P 值 10−50）。单独使用 Dlg2 中的第二个重复项，对 wormpep18 数据库进行额外的 BLASTP 搜索，显示与 Lin-7 蛋白的弱相似性（E 值 0.1）。在 Lin-7 中，匹配区域也位于 N 末端，后面是 PDZ 结构域。相似性的重要性不仅得到生物学背景的支持，还得到多重比对分析的支持（详细信息参见图1的图例）
Membrane-associated guanylate kinases (MAGUKs) are emerging as pivotal for the organization of cell-surface proteins and their interaction with the cytoskeleton 1. They are involved in cell junction organization and tumour suppression. Recent work has indicated that the Caenorhabditis elegans MAGUK protein Lin-2 is crucial for the proper targeting of the worm growth factor receptor Let-23 to the basolateral surface of epithelial cells 2. Lin-7 and Lin-10 are also required for the basolateral targeting of this receptor in worm and form a complex with Lin-2 (Ref. 3). Mammalian Lin-7 (or Veli) 4 has also been found to associate with several other smaller Lin-2 related MAGUK proteins including Dlg2, Dlg3, Pals1 and Pals2 (Ref. 5).Lin-2 and Lin-7-related proteins contain a PDZ domain (ie domain present in PSD-95, dlg and ZO-1/2), which is not involved in complex formation with the other Lin proteins 3, 4. PSI-BLAST searches 6 with the N-terminal region preceding the PDZ domain 7 of Dlg2 retrieved all members of the Lin-2 family of MAGUKS. DOTPLOT 8 two-dimensional visual comparison analysis of these proteins indicates an internal duplication, which is confirmed by MACAW alignment analysis 9 (P value 10− 50). Using the second duplicate alone in Dlg2, additional BLASTP searches against the wormpep18 database show weak similarity (E value 0.1) to the Lin-7 protein. In Lin-7, the matching region is also located at the N-terminus and is followed by a PDZ domain. The significance of the similarity is not only supported by the biological context, but also by analysis of the multiple alignment (for details, see legend of Fig. 1)