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 HIV 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 β-sheet (Ser29–Thr34; Gly42–Thr47; Gln52–Asp56). Following the sheet is a C-terminal α-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 β-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.
