Hayashi Ikuko, Vuori Kristiina, Liddington Robert C
Program on Cell Adhesion, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California 92037,USA.
Nat Struct Biol. 2002 Feb;9(2):101-6. doi: 10.1038/nsb755.
Focal adhesion kinase (FAK) is a tyrosine kinase found in focal adhesions, intracellular signaling complexes that are formed following engagement of the extracellular matrix by integrins. The C-terminal 'focal adhesion targeting' (FAT) region is necessary and sufficient for localizing FAK to focal adhesions. We have determined the crystal structure of FAT and show that it forms a four-helix bundle that resembles those found in two other proteins involved in cell adhesion, alpha-catenin and vinculin. The binding of FAT to the focal adhesion protein, paxillin, requires the integrity of the helical bundle, whereas binding to another focal adhesion protein, talin, does not. We show by mutagenesis that paxillin binding involves two hydrophobic patches on opposite faces of the bundle and propose a model in which two LD motifs of paxillin adopt amphipathic helices that augment the hydrophobic core of FAT, creating a six-helix bundle.
粘着斑激酶（FAK）是一种酪氨酸激酶，存在于粘着斑中，粘着斑是整合素与细胞外基质结合后形成的细胞内信号复合体。C末端的“粘着斑靶向”（FAT）区域对于将FAK定位到粘着斑是必要且充分的。我们已经确定了FAT的晶体结构，并表明它形成了一个四螺旋束，类似于在另外两种参与细胞粘附的蛋白质α-连环蛋白和纽蛋白中发现的螺旋束。FAT与粘着斑蛋白桩蛋白的结合需要螺旋束的完整性，而与另一种粘着斑蛋白踝蛋白的结合则不需要。我们通过诱变表明，桩蛋白结合涉及束相对面上的两个疏水斑块，并提出了一个模型，其中桩蛋白的两个LD基序采用两亲性螺旋，增强了FAT的疏水核心，形成了一个六螺旋束。
