Fernandez E J, Wilken J, Thompson D A, Peiper S C, Lolis E
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Biochemistry. 2000 Oct 24;39(42):12837-44. doi: 10.1021/bi001166f.
Herpesvirus-8 macrophage inflammatory protein-II (vMIP-II) binds a uniquely wide spectrum of chemokine receptors. We report the X-ray structure of vMIP-II determined to 2.1 A resolution. Like RANTES, vMIP-II crystallizes as a dimer and displays the conventional chemokine tertiary fold. We have compared the surface topology and electrostatic potential of vMIP-II to those of eotaxin-1, RANTES, and MCP-3, three CCR3 physiological agonists with known three-dimensional structures. Surface epitopes identified on RANTES to be involved in binding to CCR3 are mimicked on the eotaxin-1 and MCP-3 surface. However, the surface topology of vMIP-II in these regions is markedly different. The results presented here indicate that the structural basis for interaction with the chemokine receptor CCR3 by vMIP-II is different from that for the physiological agonists eotaxin-1, RANTES, and MCP-3. These differences on vMIP-II may be a consequence of its broad-range receptor recognition capabilities.
疱疹病毒8型巨噬细胞炎性蛋白-II（vMIP-II）能结合种类独特且广泛的趋化因子受体。我们报道了分辨率为2.1埃的vMIP-II的X射线晶体结构。与RANTES一样，vMIP-II以二聚体形式结晶，并呈现出传统的趋化因子三级结构。我们已将vMIP-II的表面拓扑结构和静电势与嗜酸性粒细胞趋化因子-1、RANTES和MCP-3（三种具有已知三维结构的CCR3生理性激动剂）的进行了比较。在RANTES上鉴定出的参与与CCR3结合的表面表位在嗜酸性粒细胞趋化因子-1和MCP-3表面也有类似情况。然而，vMIP-II在这些区域的表面拓扑结构明显不同。此处给出的结果表明，vMIP-II与趋化因子受体CCR3相互作用的结构基础不同于生理性激动剂嗜酸性粒细胞趋化因子-1、RANTES和MCP-3的。vMIP-II上的这些差异可能是其广泛受体识别能力的结果。
