The solution structure of the anti-HIV chemokine vMIP-II

We report the solution structure of the chemotactic cytokine (chemokine) vM IP-II. This protein has unique biological activities in that it blocks infe ction by several different human immunodeficiency virus type 1 (HIV-1) stra ins. This occurs because vMIP-II binds to a wide range of chemokine recepto rs, some of which are used by HIV to gain cell entry. vMIP-II is a monomeri c protein, unlike most members of the chemokine family, and its structure c onsists of a disordered N-terminus, followed by a helical turn (Gln25-Leu27 ), which leads into the fu st strand of a three-stranded antiparallel beta- sheet (Ser29-Thr34; Gly42-Thr47; Gln52-Asp56). Following the sheet is a C-t erminal alpha-helix, which extends from residue Asp60 until Gln68. The fina l five residues beyond the C-terminal helix (Pro70-Arg74) are in an extende d conformation, but several of these C-terminal residues contact the first P-strand. The structure of vMIP-II is compared to other chemokines that als o block infection by HIV-I, and the structural basis of its lack of ability to form a dimer is discussed.