Structures of CD6 and Its Ligand CD166 Give Insight into Their Interaction.
Structures of CD6 and Its Ligand CD166 Give Insight into Their Interaction.
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DOI：
10.1016/j.str.2015.05.019
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发表时间：
2015-08-04
期刊：
影响因子：
--
通讯作者：
Brown MH
中科院分区：
文献类型：
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作者：
Chappell PE;Garner LI;Yan J;Metcalfe C;Hatherley D;Johnson S;Robinson CV;Lea SM;Brown MH
CD 6是一种跨膜蛋白，其胞外区含有三个富含半胱氨酸的清道夫受体（SRCR）结构域。CD 6的膜近端结构域结合另一种细胞表面受体CD 166的N-末端免疫球蛋白超家族（IgSF）结构域，其也参与嗜同性相互作用。CD 6的表达主要局限于T细胞，并且CD 6和CD 166之间的相互作用调节T细胞活化。我们已经解决了CD 6的三个SRCR结构域和CD 166的两个N-末端结构域的X-射线晶体结构。连续SRCR结构域的第一种结构揭示了非线性组织。我们表征了CD 6和CD 166上的结合位点，并表明CD 6中的SNP导致阻碍CD 6/CD 166相互作用的糖基化。天然质谱分析表明，在嗜异性和嗜同性相互作用之间存在竞争。这些数据提供了洞察连续SRCR结构域的相互作用是如何被SNP和潜在的治疗试剂干扰的。CD 6中连续清道夫受体富含半胱氨酸的结构域的第一个结构CD 166的两个N-末端结构域的结构是CD 6的配体绘制CD 6和CD 166上的结合位点洞察CD 6及其相互作用如何被多态性和mAb干扰Chappell et al.展示了T细胞表面受体CD 6的结构，第一个连续的清道夫受体富含半胱氨酸的结构域及其配体CD 166。这些结构让我们深入了解CD 6及其相互作用如何受到嗜同性和嗜异性相互作用、SNP和mAb之间竞争的干扰。
CD6 is a transmembrane protein with an extracellular region containing three scavenger receptor cysteine rich (SRCR) domains. The membrane proximal domain of CD6 binds the N-terminal immunoglobulin superfamily (IgSF) domain of another cell surface receptor, CD166, which also engages in homophilic interactions. CD6 expression is mainly restricted to T cells, and the interaction between CD6 and CD166 regulates T-cell activation. We have solved the X-ray crystal structures of the three SRCR domains of CD6 and two N-terminal domains of CD166. This first structure of consecutive SRCR domains reveals a nonlinear organization. We characterized the binding sites on CD6 and CD166 and showed that a SNP in CD6 causes glycosylation that hinders the CD6/CD166 interaction. Native mass spectrometry analysis showed that there is competition between the heterophilic and homophilic interactions. These data give insight into how interactions of consecutive SRCR domains are perturbed by SNPs and potential therapeutic reagents. First structure of consecutive scavenger receptor cysteine rich domains in CD6 Structure of the two N-terminal domains of CD166 which is the ligand for CD6 Mapping binding sites on CD6 and CD166 Insight into how CD6 and its interactions are perturbed by polymorphisms and mAbs Chappell et al. present structures of the T-cell surface receptor, CD6, the first of consecutive scavenger receptor cysteine rich domains and its ligand, CD166. The structures give insight into how CD6 and its interactions are perturbed by competition between homophilic and heterophilic interactions, SNPs, and mAbs.