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.