Dual GPCR and GAG mimicry by the M3 chemokine decoy receptor.
Dual GPCR and GAG mimicry by the M3 chemokine decoy receptor.
复制标题
通过M3趋化因子诱饵受体的双重GPCR和GAG模仿。
DOI：
10.1084/jem.20071677
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发表时间：
2007-12-24
影响因子：
15.3
通讯作者：
Fremont, Daved H
中科院分区：
文献类型：
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作者：
Alexander-Brett, Jennifer M;Fremont, Daved H
病毒已经进化出无数的逃避策略，这些策略集中于破坏趋化因子介导的免疫监视，例如小鼠γ-疱疹病毒68 M3诱饵受体。M3与C趋化因子配体1/趋化蛋白和CC趋化因子配体2/单核细胞趋化蛋白1复合物的晶体结构表明，与G蛋白偶联受体结合相关的不变趋化因子特征主要由诱饵C-末端结构域识别，而N-末端结构域（NTD）重新配置以接合趋化因子表面上的不同碱性残基簇。有利的静电力显着增强M3的趋化因子结合的缔合动力学，主要作用归因于酸性NTD区域，有效地模拟糖胺聚糖相互作用。因此，M3采用两种不同的化学模拟机制来有效地螯合趋化因子，从而抑制趋化因子受体结合事件以及定向白细胞运输所必需的趋化梯度的形成。
Viruses have evolved a myriad of evasion strategies focused on undermining chemokine-mediated immune surveillance, exemplified by the mouse γ-herpesvirus 68 M3 decoy receptor. Crystal structures of M3 in complex with C chemokine ligand 1/lymphotactin and CC chemokine ligand 2/monocyte chemoattractant protein 1 reveal that invariant chemokine features associated with G protein–coupled receptor binding are primarily recognized by the decoy C-terminal domain, whereas the N-terminal domain (NTD) reconfigures to engage divergent basic residue clusters on the surface of chemokines. Favorable electrostatic forces dramatically enhance the association kinetics of chemokine binding by M3, with a primary role ascribed to acidic NTD regions that effectively mimic glycosaminoglycan interactions. Thus, M3 employs two distinct mechanisms of chemical imitation to potently sequester chemokines, thereby inhibiting chemokine receptor binding events as well as the formation of chemotactic gradients necessary for directed leukocyte trafficking.