STRUCTURE OF THE CARBOXYL-TERMINAL DIMERIZATION DOMAIN OF THE HIV-1 CAPSID PROTEIN

The carboxyl-terminal domain, residues 146 to 231, of the human immuno deficiency virus-1 (HIV-1) capsid protein [CA(146-231)] is required fo r capsid dimerization and viral assembly. This domain contains a stret ch of 20 residues, called the major homology region (MHR), which is co nserved across retroviruses and is essential for viral assembly, matur ation, and infectivity. The crystal structures of CA(146-231) and CA(1 51-231) reveal that the globular domain is composed of four helices an d an extended aminoterminal strand. CA(146-231) dimerizes through para llel packing of helix 2 across a dyad. The MHR is distinct from the di mer interface and instead forms an intricate hydrogen-bonding network that interconnects strand 1 and helices 1 and 2. Alignment of the CA(1 46-231) dimer with the crystal structure of the capsid amino-terminal domain provides a model for the intact protein and extends models for assembly of the central conical core of HIV-1.