Chemokines are critical mediators of cell migration during routine immune surveillance, inflammation, and development. Chemokines bind to G protein-coupled receptors and cause conformational changes that trigger intracellular signaling pathways involved in cell movement and activation. Although chemokines evolved to benefit the host, inappropriate regulation or utilization of these proteins can contribute to or cause many diseases. Specific chemokine receptors provide the portals for HIV to get into cells, and others contribute to inflammatory diseases and cancer. Thus, there is significant interest in developing receptor antagonists. To this end, the structures of ligands coupled with mutagenesis studies have revealed mechanisms for antagonism based on modified proteins. Although little direct structural information is available on the receptors, binding of small molecules to mutant receptors has allowed the identification of key residues involved in the receptor-binding pockets. In this review, we discuss the current knowledge of chemokine:receptor structure and function, and its contribution to drug discovery.

中文翻译：

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趋化因子：受体结构，相互作用和拮抗作用。

趋化因子是常规免疫监测，炎症和发育过程中细胞迁移的关键介质。趋化因子与G蛋白偶联受体结合并引起构象变化，从而触发参与细胞运动和活化的细胞内信号传导途径。尽管趋化因子进化为有益于宿主，但是这些蛋白的不适当调节或利用会导致或引起许多疾病。特定的趋化因子受体为HIV提供进入细胞的门户，而其他趋化因子则导致炎症性疾病和癌症。因此，对开发受体拮抗剂有极大的兴趣。为此，配体的结构与诱变研究相结合，揭示了基于修饰蛋白的拮抗机制。尽管几乎没有关于受体的直接结构信息，小分子与突变受体的结合已经允许鉴定参与受体结合口袋的关键残基。在这篇综述中，我们讨论了趋化因子：受体结构和功能的最新知识，及其对药物发现的贡献。