Structures of the HIV-1 capsid protein dimerization domain at 2.6 Å 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 Å resolution to R factors of 22.3 and 20.7% (R_free = 28.1 and 27.5%), respectively. The ordered domains comprise residues 148–219 for CA_146–231 and 148–218 for CA_146–p2, and their refined structures are essentially identical. The proteins are composed of a 3₁₀ helix followed by an extended strand and four α-helices. A crystallographic twofold generates a dimer that is stabilized by parallel packing of an α-­helix 2 across the dimer interface and by packing of the 3₁₀ helix into a groove created by α-­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.