SDF-1和及其受体CXCR4的结构与功能

The Structure and Function of SDF-1 and Its Receptor CXCR4

近年基质细胞衍生因子 1(SDF 1)及其受体CXCR4的构效关系与相互作用机制研究进展很快 .研究证实 ,SDF 1N末端 (Nt)氨基酸残基是与CXCR4相互作用的关键区域 .SDF 1的 β链与蛋白聚糖 (GAG)作用而调节SDF 1的功能 ,C端α螺旋有助于维持SDF 1的活性构象 ;CXCR4Nt、ECL2和 (或 )ECL3对于SDF 1和HIVgp12 0对CXCR4的识别和激活都很重要 ,但在识别序列上存在部分交叉重叠 .SDF 1 CXCR4与肿瘤转移密切相关 ,本文还就SDF 1与CXCR4在肿瘤治疗方面的应用进行了讨论 .

The structure and function relationship of stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 have been studied widely in recent years. It was demonstrated that the N-terminus(Nt) of SDF-1 was the critical region for its interaction with CXCR4, the β-sheets modulated the activity of SDF-1 by interacting with glycosaminoglycan (GAG) and the C-terminal(Ct) α-helix was required to maintain the active conformation of SDF-1. It was also found that Nt and the second extracellular loop (ECL2) and/or ECL3 of CXCR4 played an important role in SDF-1 and HIV gp120 recognizing process, but the recognizing sequences were partially overlapped. SDF-1-CXCR4 pair was specifically involved in cancer cell metastasis and the application of SDF-1 to inhibit cancer cell metastasis was also discussed.