Encoded by Kaposi's sarco
ma-associated herpesvirus, viral
macrophage-inflam
matory protein-II (VMIP-II) is unique among CC chemokines in that it has been shown to bind to the CXC chemokinereceptor CXCR4 as well as to a variety of CC chemokine receptors. This unique binding ability allowsvMIP-II to block infection by a wide range of hu
man immunodeficiency virus type I (HIV-1) strains, butthe structural and dynamic basis for this broad range of binding is not known.
15N
T1,
T2 and
15N{-H
N}nuclear Overhauser effect (NOE) values of vMIP-II, determined through a series of heteronuclearmultidimensional nuclear
magnetic resonance (NMR) experiments, were used to obtain infor
mation aboutthe backbone dynamics of the protein. Whereas almost all chemokine structures reveal a dimer or multimer,vMIP-II has a rotational correlation time (
mages/gifchars/tau.gif" BORDER=0 >
c) of 4.7 ± 0.3 ns, which is consistent with a monomericchemokine. The rotational diffusion anisotropy,
Dmages/entities/par.gif">/
Dmages/entities/bottom.gif">, is approxi
mately 1.5 ± 0.1. The confor
mation ofvMIP-II is quite similar to other known chemokines, containing an unstructured N-terminus followed byan ordered turn, three
mages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-strands arranged in an antiparallel fashion, and one C-terminal
mages/gifchars/alpha.gif" BORDER=0>-helix that liesacross the
mages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-strands. Most of the protein is well-ordered on a picosecond time scale, with an averageorder parameter
S2 (excluding the N-terminal 13 amino acids) of 0.83 ± 0.09, and with even greaterorder in regions of secondary structure. The NMR data reveal that the N-terminus, which in otherchemokines has been implicated in receptor binding, extends like a flexible tail in solution and possessesno secondary structure. The region of the ordered turn, including residues 25-28, experiencesconfor
mational exchange dynamics. The implications of these NMR data to the broad receptor bindingcapability of vMIP-II are discussed.