Structures of the HIV-1 capsid protein dimerization domain at 2.6Å resolution

The human immunodeficiency virus type I (HIV-1) capsid protein is initially synthesized as the central domain of the Gag polyprotein, and is subsequently proteolytically processed into a discrete 231-amino-acid protein that forms the distinctive conical core of the mature virus. The crystal structures of two proteins that span the C-terminal domain of the capsid are reported here: one encompassing residues 146-231 (CA(146-231)) and the other extending to include the 14-residue p2 domain of Gag (CA(146-p2)). The isomorphous CA(146-231) and CA(146-p2) structures were determined by molecular replacement and have been refined at 2.6 Angstrom resolution to R factors of 22.3 and 20.7% (Re-free = 28.1 and 27.5%), respectively. The ordered domains comprise residues 148-219 for CA(146-231) and 14-218 for CA(146-p2), and their refined structures are essentially identical. The proteins are composed of a 3(10) helix followed by an extended strand and four alpha-helices. A crystallographic twofold generates a dimer that is stabilized by parallel packing of an alpha-helix 2 across the dimer interface and by packing of the 310 helix into a groove created by alpha-helices 2 and 3 of the partner molecule. CA(146-231) and CA(146-p2) dimerize with the full affinity of the intact capsid protein, and their structures therefore reveal the essential dimer interface of the HIV-1 capsid.