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 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.