CCR2 and CCR5 receptorâbinding properties of herpesvirusâ8 vMIPâII based on sequence analysis and its solution structure
2001
Shao, Weiping | Fernandez, Elias | Sachpatzidis, Aristidis | Wilken, Jill | Thompson, Darren A. | Schweitzer, Barry I. | Lolis, Elias
Human herpesvirusâ8 (HHVâ8) is the infectious agent responsible for Kaposi’s sarcoma and encodes a protein, macrophage inflammatory proteinâII (vMIPâII), which shows sequence similarity to the human CC chemokines. vMIPâII has broad receptor specificity that crosses chemokine receptor subfamilies, and inhibits HIVâ1 viral entry mediated by numerous chemokine receptors. In this study, the solution structure of chemically synthesized vMIPâII was determined by nuclear magnetic resonance. The protein is a monomer and possesses the chemokine fold consisting of a flexible Nâterminus, three antiparallel β strands, and a Câterminal α helix. Except for the Nâterminal residues (residues 1–13) and the last two Câterminal residues (residues 73–74), the structure of vMIPâII is wellâdefined, exhibiting average rmsd of 0.35 and 0.90âà for the backbone heavy atoms and all heavy atoms of residues 14–72, respectively. Taking into account the sequence differences between the various CC chemokines and comparing their threeâdimensional structures allows us to implicate residues that influence the quaternary structure and receptor binding and activation of these proteins in solution. The analysis of the sequence and threeâdimensional structure of vMIPâII indicates the presence of epitopes involved in binding two receptors CCR2 and CCR5. We propose that vMIPâII was initially specific for CCR5 and acquired receptorâbinding properties to CCR2 and other chemokine receptors.
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