The solution structure of the anti-HIV chemokine vMIP-II.
We report the solution structure of the chemotactic cytokine (chemokine) vMIP-II. This protein has unique biological activities in that it blocks infection by several different human immunodeficiency virus type 1 (HIV-1) strains. This occurs because vMIP-II binds to a wide range of chemokine receptors, some of which are used by HJV to gain cell entry. vMIP-II is a monomeric protein, unlike most members of the chemokine family, and its structure consists of a disordered N-terminus, followed by a helical turn (Gln25-Leu27), which leads into the first strand of a three-stranded antiparallel beta-sheet (Ser29-Thr34; Gly42-Thr47; Gln52-Asp56). Following the sheet is a C-terminal alpha-helix, which extends from residue Asp60 until Gln68. The final five residues beyond the C-terminal helix (Pro70-Arg74) are in an extended conformation, but several of these C-terminal residues contact the first beta-strand. The structure of vMIP-II is compared to other chemokines that also block infection by HIV-1, and the structural basis of its lack of ability to form a dimer is discussed.
Liwang
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AC
Texas A&M University, Department of Biochemistry and Biophysics, College Station 77843-2128, USA.
Wang
Z X
ZX
Sun
Y
Y
Peiper
S C
SC
Liwang
P J
PJ
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000737:chemistry*; D054413:Chemokine CCL11; D054407:Chemokine CCL4; D054377:Chemokine CXCL12; D018925:Chemokines / Q000737:chemistry* / Q000494:pharmacology; D019742:Chemokines, CC / Q000737:chemistry*; D019743:Chemokines, CXC / Q000737:chemistry; D002631:Chemotactic Factors, Eosinophil / Q000737:chemistry; D016207:Cytokines / Q000737:chemistry; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012996:Solutions
D019380:Anti-HIV Agents; C515456:CCL11 protein, human; C515255:CXCL12 protein, human; D054413:Chemokine CCL11; D054407:Chemokine CCL4; D054377:Chemokine CXCL12; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D012996:Solutions; C108059:vMIP-II