The structural basis of localization and signaling by the focal adhesion targeting domain
The structural basis of localization and signaling by the focal adhesion targeting domain
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DOI：
10.1016/s0969-2126(02)00717-7
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发表时间：
2002-03-01
期刊：
影响因子：
5.7
通讯作者：
Noble, MEM
中科院分区：
文献类型：
--
作者：
Arold, ST;Hoellerer, MK;Noble, MEM
粘着斑激酶（FAK）定位于整合素聚集的位点启动下游信号传导。C-末端粘着斑靶向（FAT）结构域通过与talin和桩蛋白相互作用引起这种定位。FAT还通过磷酸化的Y 925介导Grb 2的信号传导。我们报告两个晶体结构的FAT域。结构的大重排被指示允许Y 925的磷酸化和随后与Grb 2的相互作用。序列同源性和结构相容性表明CAS，Efs/Sin和HEF 1的C-末端结构域具有FAT样折叠。一个基于结构的比对，包括这些蛋白质和黏着斑蛋白尾部结构域揭示了一个保守的区域，可以发挥作用的粘着斑靶向。以前假设的“桩蛋白结合亚结构域”可能有助于结构完整性，而不是直接桩蛋白结合。
The localization of focal adhesion kinase (FAK) to sites of integrin clustering initiates downstream signaling. The C-terminal focal adhesion targeting (FAT) domain causes this localization by interacting with talin and paxillin. FAT also mediates signaling through Grb2 via phosphorylated Y925. We report two crystal structures of the FAT domain. Large rearrangements of the structure are indicated to allow phosphorylation of Y925 and subsequent interaction with Grb2. Sequence homology and structural compatibility suggest a FAT-like fold for the C-terminal domains of CAS, Efs/Sin, and HEF1. A structure-based alignment including these proteins and the vinculin tail domain reveals a conserved region that could play a role in focal adhesion targeting. Previously postulated "paxillin binding subdomains" may contribute to structural integrity rather than directly to paxillin binding.