Comparison of the structure of vMIP-II with eotaxin-1, RANTES, and MCP-3 suggests a unique mechanism for CCR3 activation

Herpesvirus-X macrophage inflammatory protein-II (vMIP-II) binds a uniquely wide spectrum of chemokine receptors. We report the X-ray structure of vMI P-II determined to 2.1 Angstrom resolution. Like RANTES, vMIP-II crystalliz es as a dimer and displays the conventional chemokine tertiary fold. We hav e compared the surface topology and electrostatic potential of vMIP-II to t hose 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 s urface. However, the surface topology of vMIP-II in these regions is marked ly different. The results presented here indicate that the structural basis for interaction with the chemokine receptor CCR3 by vMIP-II is different f rom 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 re cognition capabilities.