Crystal structures of free and ligand-bound focal adhesion targeting domain of Pyk2
Crystal structures of free and ligand-bound focal adhesion targeting domain of Pyk2
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DOI：
10.1016/j.bbrc.2009.04.011
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发表时间：
2009-06-05
影响因子：
3.1
通讯作者：
Schlessinger, Joseph
中科院分区：
文献类型：
--
作者：
Lulo, James;Yuzawa, Satoru;Schlessinger, Joseph
粘着斑靶向(FAT)结构域将非受体酪氨酸激酶FAK和PYK2靶向细胞粘着斑区，信号分子Paxlin也位于该区域。在这里，我们报告了单独的或与巴西林LD4多肽复合的Pyk2脂肪域的晶体结构。Pyk2-FAT的整体结构是一个反平行的四螺旋束，具有上下、唇下、右手的拓扑结构。在LD4结合的脂肪复合体中，在每个脂肪分子的α1α4和α2α3螺旋的表面，两个巴西林LD4多肽与PYK2-FAT的两个相反的侧面相互作用。我们还证明，虽然帕克西林被PYK2磷酸化，但PYK2和PXLIN之间的复合体的形成并不依赖于PYK2酪氨酸激酶的活性。这些实验揭示了帕克西林LD4与Pyk2脂肪域结合的选择性的结构基础，并为影响这两个密切相关的激酶不同行为的分子细节提供了见解。(C)2009 Elsevier Inc.保留所有权利。
Focal adhesion targeting (FAT) domains target the non-receptor tyrosine kinases FAK and Pyk2 to cellular focal adhesion areas, where the signaling molecule paxillin is also located. Here, we report the crystal Structures of the Pyk2 FAT domain alone or in complex with paxillin LD4 peptides. The overall Structure of Pyk2-FAT is an antiparallel four-helix bundle with an up-down, Lip-down, right-handed topology. In the LD4-bound FAT complex, two paxillin LD4 peptides interact with two opposite sides of Pyk2-FAT, at the Surfaces of the alpha 1 alpha 4 and alpha 2 alpha 3 helices of each FAT molecule. We also demonstrate that, while paxillin is phosphorylated by Pyk2, complex formation between Pyk2 and paxillin does not depend on Pyk2 tyrosine kinase activity. These experiments reveal the structural basis underlying the selectivity of paxillin LD4 binding to the Pyk2 FAT domain and provide insights about the molecular details which influence the different behavior of these two closely-related kinases. (C) 2009 Elsevier Inc. All rights reserved.