Transferring the C-terminus of the chemokine CCL21 to CCL19 confers enhanced heparin binding.
Transferring the C-terminus of the chemokine CCL21 to CCL19 confers enhanced heparin binding.
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DOI：
10.1016/j.bbrc.2016.06.098
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发表时间：
2016-09-02
影响因子：
3.1
通讯作者：
Veldkamp CT
中科院分区：
文献类型：
--
作者：
Barmore AJ;Castex SM;Gouletas BA;Griffith AJ;Metz SW;Muelder NG;Populin MJ;Sackett DM;Schuster AM;Veldkamp CT
趋化因子在各种免疫过程中指导细胞的迁移，并参与许多疾病状态。例如，CCL19和CCL21通过激活CCR7受体，将树突状细胞和naïve t细胞招募到次级淋巴器官，帮助平衡免疫反应和耐受。然而，CCL19和CCL21也可以指导表达CCR7的癌症的转移。趋化因子与糖胺聚糖结合，如肝素，对趋化因子的功能和受体激活同样重要。CCL21的独特之处在于它包含一个在其他趋化因子如CCL19中没有发现的延长的c端。删除这个延长的c端会降低CCL21对肝素的亲和力，将CCL21的c端转移到CCL19上，主要通过非特异性的静电相互作用增强肝素的结合。
Chemokines direct the migration of cells during various immune processes and are involved in many disease states. For example, CCL19 and CCL21, through activation of the CCR7 receptor, recruit dendritic cells and naïve T-cells to the secondary lymphoid organs aiding in balancing immune response and tolerance. However, CCL19 and CCL21 can also direct the metastasis of CCR7 expressing cancers. Chemokine binding to glycosaminoglycans, such as heparin, is as important to chemokine function as receptor activation. CCL21 is unique in that it contains an extended C-terminus not found in other chemokines like CCL19. Deletion of this extended C-terminus reduces CCL21’s affinity for heparin and transferring the CCL21 C-terminus to CCL19 enhances heparin binding mainly through non-specific, electrostatic interactions.