Structural basis for the interaction between the cytoplasmic domain of the hyaluronate receptor layilin and the talin F3 subdomain
Structural basis for the interaction between the cytoplasmic domain of the hyaluronate receptor layilin and the talin F3 subdomain
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DOI：
10.1016/j.jmb.2008.06.087
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发表时间：
2008-09-26
影响因子：
5.6
通讯作者：
Barsukov, Igor L.
中科院分区：
文献类型：
--
作者：
Wegener, Kate L.;Basran, Jaswir;Barsukov, Igor L.
Talin是一种大的细胞骨架蛋白，参与将细胞粘附分子的整合素家族偶联到肌动蛋白细胞骨架上，并在局灶性粘附（FAs）中与整合素共定位。然而，在运动细胞的前沿，talin与透明质酸受体层蛋白共定位，被认为是短暂的粘连，其中一些随后成熟为更稳定的FAs。在这一成熟过程中，layilin被整合素取代，整合素在FAs中高度聚集，在FAs中，1型磷脂酰肌醇磷酸激酶1型γ (PIPK1 γ)局部产生PI(4,5)P-2被认为在FA组装中发挥作用。talin FERM F3亚结构域结合整合素β亚基细胞质结构域和PIPK1 γ，这些相互作用在原子水平上得到了详细的理解。talin F3结构域也与layilin细胞质结构域的短序列结合，这里我们报道了talin/layilin复合物的结构，这表明talin以相似的方式结合整合素、PIPK1 γ和layilin，尽管有细微的不同。基于结构比较，我们设计了一组talin F3突变，这些突变选择性地影响talin对其靶标的亲和力，这是通过停止流动荧光测量确定的。这些突变将有助于评估talin及其各种配体在细胞粘附和迁移中的相互作用的重要性。(C) 2008 Elsevier Ltd版权所有。
Talin is a large cytoskeletal protein that is involved in coupling the integrin family of cell adhesion molecules to the actin cytoskeleton, colocalising with the integrins in focal adhesions (FAs). However, at the leading edge of motile cells, talin colocalises with the hyaluronan receptor layilin in what are thought to be transient adhesions, some of which subsequently mature into more stable FAs. During this maturation process, layilin is replaced with integrins, which are highly clustered in FAs, where localised production of PI(4,5)P-2 by type 1 phosphatidyl inositol phosphate kinase type 1 gamma (PIPK1 gamma) is thought to play a role in FA assembly. The talin FERM F3 subdomain binds both the integrin beta-subunit cytoplasmic domain and PIPK1 gamma, and these interactions are understood in detail at the atomic level. The talin F3 domain also binds to short sequences in the layilin cytoplasmic domain, and here we report the structure of the talin/layilin complex, which shows that talin binds integrins, PIPK1 gamma and layilin in similar although subtly different ways. Based on structure comparisons, we designed a set of talin F3 mutations that selectively affected the affinity of talin for its targets, as determined by stopped-flow fluorescence measurements. Such mutations will help to assess the importance of the interactions between talin and its various ligands in cell adhesion and migration. (C) 2008 Elsevier Ltd. All rights reserved.