Characterization of 14-3-3-ζ Interactions with integrin tails.
Characterization of 14-3-3-ζ Interactions with integrin tails.
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14-3-3-ζ 与整合素尾部相互作用的表征。
DOI：
10.1016/j.jmb.2013.05.024
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发表时间：
2013-09-09
影响因子：
5.6
通讯作者：
Campbell, Iain D.
中科院分区：
文献类型：
--
作者：
Bonet, Roman;Vakonakis, Ioannis;Campbell, Iain D.
整合素是异二聚体(α+β)黏附受体家族，在许多细胞过程中发挥关键作用。整合素的不同寻常之处在于，它们的功能可以从细胞内外调节。内向外信号是通过将接头蛋白与α-和β-整合素亚基的灵活胞质尾部结合而介导的。Talin是一种众所周知的细胞内激活剂，但各种其他适配器与整合素尾巴结合，包括14-3-3-ζ，它是14-3-3二聚体蛋白家族的成员，喜欢结合磷酸化的序列基序。β-2整合素尾部苏氨酸的磷酸化可调节β-2/14-3-3-ζ的相互作用，最近报道α-4整合素尾部与14-3-3-ζ结合，并与帕西林形成三元复合体，受丝氨酸磷酸化调控。在这里，我们使用一系列生物物理技术来表征14-3-3-ζ与α4、β1、β2和β3整合素的细胞质尾部之间的相互作用。14-3-3-ζ/α4复合体的X射线结构表明α4磷酸肽具有典型的结合模式，但也观察到了意想不到的特征：14-3-3-ζ结合基序之外的残基被证明是有效相互作用所必需的；相比之下，短的β2磷酸肽足以与14-3-3-ζ高亲和力结合。此外，我们报道了新的14-3-3-ζ/整合素尾部相互作用，这种相互作用不依赖于磷酸化。在所研究的整合素尾巴中，观察到与14-3-3-ζ相互作用最强的是β1A变异体。综上所述，关于14-3-3-ζ/整合素尾部相互作用的新见解对这些分子结合在细胞中的作用具有意义。整合素的尾巴对于跨膜的双向信号很重要。用生物物理技术研究了14-3-3-ζ与整合素尾部的结合。14-3-3结合基序外的残基有助于α4的亲和力，而不是β2的亲和力。已有报道14-3-3-ζ与整合素尾部的相互作用不依赖于磷酸化。
Integrins are a family of heterodimeric (α+β) adhesion receptors that play key roles in many cellular processes. Integrins are unusual in that their functions can be modulated from both outside and inside the cell. Inside-out signaling is mediated by binding adaptor proteins to the flexible cytoplasmic tails of the α- and β-integrin subunits. Talin is one well-known intracellular activator, but various other adaptors bind to integrin tails, including 14-3-3-ζ, a member of the 14-3-3 family of dimeric proteins that have a preference for binding phosphorylated sequence motifs. Phosphorylation of a threonine in the β2 integrin tail has been shown to modulate β2/14-3-3-ζ interactions, and recently, the α4 integrin tail was reported to bind to 14-3-3-ζ and associate with paxillin in a ternary complex that is regulated by serine phosphorylation. Here, we use a range of biophysical techniques to characterize interactions between 14-3-3-ζ and the cytoplasmic tails of α4, β1, β2 and β3 integrins. The X-ray structure of the 14-3-3-ζ/α4 complex indicates a canonical binding mode for the α4 phospho-peptide, but unexpected features are also observed: residues outside the consensus 14-3-3-ζ binding motif are shown to be essential for an efficient interaction; in contrast, a short β2 phospho-peptide is sufficient for high-affinity binding to 14-3-3-ζ. In addition, we report novel 14-3-3-ζ/integrin tail interactions that are independent of phosphorylation. Of the integrin tails studied, the strongest interaction with 14-3-3-ζ is observed for the β1A variant. In summary, new insights about 14-3-3-ζ/integrin tail interactions that have implications for the role of these molecular associations in cells are described. Integrin tails are important for bidirectional signaling across the membrane. 14-3-3-ζ binding to integrin tails has been studied using biophysical techniques. Residues outside the 14-3-3 binding motif contribute to affinity in α4 but not in β2. Phosphorylation-independent 14-3-3-ζ interactions with integrin tails are reported.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
4.8
作者：
Han, JW;Liu, SC;Ginsberg, MH
通讯作者：
Ginsberg, MH
影响因子：
4.8
作者：
Fuglsang, AT;Visconti, S;Palmgren, MG
通讯作者：
Palmgren, MG
影响因子：
14.9
作者：
Davis IW;Leaver-Fay A;Chen VB;Block JN;Kapral GJ;Wang X;Murray LW;Arendall WB 3rd;Snoeyink J;Richardson JS;Richardson DC
通讯作者：
Richardson DC
影响因子：
2.7
作者：
BARTELS, C;XIA, TH;WUTHRICH, K
通讯作者：
WUTHRICH, K