title: Dynamics study on the anti-human immunodeficiency virus chemokine viral macrophage-inflammatory protein-II (VMIP-II) reveals a fully monomeric protein.
abstract: Encoded by Kaposi's sarcoma-associated herpesvirus, viral macrophage-inflammatory protein-II (VMIP-II) is unique among CC chemokines in that it has been shown to bind to the CXC chemokine receptor CXCR4 as well as to a variety of CC chemokine receptors. This unique binding ability allows vMIP-II to block infection by a wide range of human immunodeficiency virus type I (HIV-1) strains, but the structural and dynamic basis for this broad range of binding is not known. 15N T1, T2 and 15N[-HN] nuclear Overhauser effect (NOE) values of vMIP-II, determined through a series of heteronuclear multidimensional nuclear magnetic resonance (NMR) experiments, were used to obtain information about the backbone dynamics of the protein. Whereas almost all chemokine structures reveal a dimer or multimer, vMIP-II has a rotational correlation time (tauc) of 4.7 +/- 0.3 ns, which is consistent with a monomeric chemokine. The rotational diffusion anisotropy, D parallel/D perpendicular, is approximately 1.5 +/- 0.1. The conformation of vMIP-II is quite similar to other known chemokines, containing an unstructured N-terminus followed by an ordered turn, three beta-strands arranged in an antiparallel fashion, and one C-terminal alpha-helix that lies across the beta-strands. Most of the protein is well-ordered on a picosecond time scale, with an average order parameter S2 (excluding the N-terminal 13 amino acids) of 0.83 +/- 0. 09, and with even greater order in regions of secondary structure. The NMR data reveal that the N-terminus, which in other chemokines has been implicated in receptor binding, extends like a flexible tail in solution and possesses no secondary structure. The region of the ordered turn, including residues 25-28, experiences conformational exchange dynamics. The implications of these NMR data to the broad receptor binding capability of vMIP-II are discussed.
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, Indiana 47907-1393, USA. liwang@chem.purdue.edu
authors.forename: A C
authors.initials: AC
authors.lastname: LiWang
authors.forename: J J
authors.initials: JJ
authors.lastname: Cao
authors.forename: H
authors.initials: H
authors.lastname: Zheng
authors.forename: Z
authors.initials: Z
authors.lastname: Lu
authors.forename: S C
authors.initials: SC
authors.lastname: Peiper
authors.forename: P J
authors.initials: PJ
authors.lastname: LiWang
mesh_terms: D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000737:chemistry*; D018925:Chemokines / Q000737:chemistry*; D019742:Chemokines, CC / Q000737:chemistry*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D009587:Nitrogen Isotopes; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013816:Thermodynamics
chemical_list: D019380:Anti-HIV Agents; D018925:Chemokines; D019742:Chemokines, CC; D009587:Nitrogen Isotopes; C108059:vMIP-II