Intrinsically disordered cytoplasmic domains of two cytokine receptors mediate conserved interactions with membranes
Intrinsically disordered cytoplasmic domains of two cytokine receptors mediate conserved interactions with membranes
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DOI：
10.1042/bj20141243
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发表时间：
2015-06-15
影响因子：
4.1
通讯作者：
Kragelund, Birthe B.
中科院分区：
文献类型：
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作者：
Haxholm, Gitte W.;Nikolajsen, Louise F.;Kragelund, Birthe B.
1 类细胞因子受体通过复杂的细胞内信号网络调节重要的生物过程。然而，由于细胞内结构域（ICD）的结构功能研究严重缺乏，目前用于理解其功能的结构平台还不完整。本研究首次提供了任何细胞因子受体 ICD 的全面结构特征，并证明人催乳素 (PRL) 受体 (PRLR) 和生长激素受体 (GHR) ICD 在其整个长度上本质上是无序的。我们证明它们通过类似于免疫受体酪氨酸激活基序（ITAM）的保守基序与内质膜小叶的标志性脂质特异性相互作用。然而，与 ITAM 的观察结果相反，PRLR 和 GHR ICD 的脂质关联不伴随瞬时二级结构的变化并且独立于酪氨酸磷酸化。本研究的结果为研究1类细胞因子受体提供了一个新的结构平台，并可能暗示膜作为调节细胞内信号传导的活性成分。
Class 1 cytokine receptors regulate essential biological processes through complex intracellular signalling networks. However, the structural platform for understanding their functions is currently incomplete as structure-function studies of the intracellular domains (ICDs) are critically lacking. The present study provides the first comprehensive structural characterization of any cytokine receptor ICD and demonstrates that the human prolactin (PRL) receptor (PRLR) and growth hormone receptor (GHR) ICDs are intrinsically disordered throughout their entire lengths. We show that they interact specifically with hallmark lipids of the inner plasma membrane leaflet through conserved motifs resembling immuno receptor tyrosine-based activation motifs (ITAMs). However, contrary to the observations made for ITAMs, lipid association of the PRLR and GHR ICDs was shown to be unaccompanied by changes in transient secondary structure and independent of tyrosine phosphorylation. The results of the present study provide a new structural platform for studying class 1 cytokine receptors and may implicate the membrane as an active component regulating intracellular signalling.