趋化因子及其受体：来自分子建模与晶体学的见解
Chemokines and their receptors: insights from molecular modeling and crystallography.
作者信息
Kufareva Irina
机构信息
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
出版信息
Curr Opin Pharmacol. 2016 Oct;30:27-37. doi: 10.1016/j.coph.2016.07.006. Epub 2016 Jul 25.
Abstract
Chemokines are small secreted proteins that direct cell migration in development, immunity, inflammation, and cancer. They do so by binding and activating specific G protein coupled receptors on the surface of migrating cells. Despite the importance of receptor:chemokine interactions, their structural basis remained unclear for a long time. In 2015, the first atomic resolution insights were obtained with the publication of X-ray structures for two distantly related receptors bound to chemokines. In conjunction with experiment-guided molecular modeling, the structures suggest a conserved receptor:chemokine complex architecture, while highlighting the diverse details and functional roles of individual interaction epitopes. Novel findings promote the development and detailed structural interpretation of the canonical two-site hypothesis of receptor:chemokine recognition, and suggest new avenues for pharmacological modulation of chemokine receptors.
摘要
趋化因子是一类分泌型小蛋白，在发育、免疫、炎症和癌症过程中指导细胞迁移。它们通过结合并激活迁移细胞表面的特定G蛋白偶联受体来实现这一功能。尽管受体与趋化因子的相互作用非常重要，但其结构基础长期以来一直不清楚。2015年，随着两种远亲受体与趋化因子结合的X射线结构的发表，首次获得了原子分辨率的见解。结合实验指导的分子建模，这些结构揭示了保守的受体-趋化因子复合物结构，同时突出了各个相互作用表位的不同细节和功能作用。新发现推动了受体-趋化因子识别的经典双位点假说的发展和详细结构解释，并为趋化因子受体的药理调节提供了新途径。
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