STRUCTURE-ACTIVITY-RELATIONSHIPS OF CHEMOKINES
STRUCTURE-ACTIVITY-RELATIONSHIPS OF CHEMOKINES
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DOI：
10.1002/jlb.57.5.703
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发表时间：
1995-05-01
影响因子：
5.5
通讯作者：
SYKES, BD
中科院分区：
文献类型：
--
作者：
CLARKLEWIS, I;KIM, KS;SYKES, BD
趋化因子的结构分析表明，在CXC和CC类趋化因子中，α/β结构折叠高度保守，尽管经常观察到二聚化和聚集，但趋化因子作为单体发挥作用，关键的受体结合区位于蛋白质的NH2末端20个残基，在溶液中是最无序的，灵活的NH2末端区域是最关键的受体结合部位，在两个二硫键之后的环中也存在第二个部位，有序的区域不直接参与受体结合，但与二硫键一起，它们提供了决定受体结合关键部位的构象的支架，这些对功能的一般要求对所有趋化因子都是共同的，因为CC趋化因子，受体激活和受体结合区在10个残基的NH2末端区域是分开的，这使得能够识别不激活受体的高亲和力类似物，而这些类似物是有效的拮抗剂。
Structural analysis of chemokines has revealed that the alpha/beta structural-fold is highly conserved among both the CXC and CC chemokine classes, Although dimerization and aggregation is often observed, the chemokines function as monomers, The critical receptor binding regions are in the NH2-terminal 20 residues of the protein and are the least ordered in solution, The flexible NH2-terminal region is the most critical receptor binding site and a second site also exists in the loop that follows the two disulfides, The well ordered regions are not directly involved in receptor binding but, along with the disulfides, they provide a scaffold that determines the conformation of the sites that are critical for receptor binding, These general requirements for function are common to all the chemokines, For the CC chemokines, receptor activation and receptor binding regions are separate within the 10 residue NH2-terminal region, This has allowed identification of high affinity analogs that do not activate the receptor and are potent antagonists.