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 (CA146–231) and the other extending to include the 14‐residue p2 domain of Gag (CA146–p2). The isomorphous CA146–231 and CA146–­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% (Rfree = 28.1 and 27.5%), respectively. The ordered domains comprise residues 148–219 for CA146–231 and 148–218 for CA146–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. CA146–231 and CA146–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.