Structural and biochemical characterization of the interaction between LGN and Frmpd1.
Structural and biochemical characterization of the interaction between LGN and Frmpd1.
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DOI：
10.1016/j.jmb.2013.01.003
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发表时间：
2013-03
影响因子：
5.6
通讯作者：
Z. Pan;Y. Shang;M. Jia;Lu Zhang;C. Xia;Mingjie Zhang;Wenning Wang;W. Wen
中科院分区：
文献类型：
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作者：
Z. Pan;Y. Shang;M. Jia;Lu Zhang;C. Xia;Mingjie Zhang;Wenning Wang;W. Wen
含有三肽重复序列（TPR）基序的蛋白质LGN结合多个靶点，并在不对称和对称细胞分裂过程中调节它们的亚细胞定位和功能。在这里，我们表征了LGN-TPR基序与FERM和PDZ结构域1（Frmpd 1）之间的相互作用，并报道了2.4 nm分辨率的复合物的晶体结构。在Frmpd 1的中心的高度保守的片段的~20个残基被发现是必要的和足够的结合LGN-TPR。该Frmpd 1片段形成延伸结构，并在复合物中以反平行方式沿着TPR超螺旋的凹通道运行。LGN/Frmpd 1和其他已知的LGN/靶标相互作用的结构比较和生物化学研究表明，LGN-TPR基序是通用的，能够通过不同的结合模式识别多种靶标。然而，在LGN/Pins（可切割的伴侣）TPR结合蛋白中，已经鉴定了保守的“E/QxEx 4 -5E/D/Qx 1 -2K/R”基序。
The tetratricopeptide repeat (TPR) motif-containing protein LGN binds multiple targets and regulates their subcellular localizations and functions during both asymmetric and symmetric cell divisions. Here, we characterized the interaction between LGN-TPR motifs and FERM and PDZ domain containing 1 (Frmpd1) and reported the crystal structure of the complex at 2.4Å resolution. A highly conserved fragment at the center of Frmpd1 of ~20 residues was found to be necessary and sufficient to bind to LGN-TPR. This Frmpd1 fragment forms an extended structure and runs along the concave channel of the TPR superhelix in an antiparallel manner in the complex. Structural comparisons and biochemical studies of LGN/Frmpd1 and other known LGN/target interactions demonstrate that the LGN-TPR motifs are versatile and capable of recognizing multiple targets via diverse binding modes. Nevertheless, a conserved “E/QxEx4-5E/D/Qx1-2K/R” motif in LGN/Pins (partner of inscuteable) TPR binding proteins has been identified.