Structure of the Carboxyl-Terminal Dimerization Domain of the HIV-1 Capsid Protein

Abstract

The carboxyl-terminal domain, residues 146 to 231, of the human immunodeficiency virus–1 (HIV-1) capsid protein [CA(146–231)] is required for capsid dimerization and viral assembly. This domain contains a stretch of 20 residues, called the major homology region (MHR), which is conserved across retroviruses and is essential for viral assembly, maturation, and infectivity. The crystal structures of CA(146–231) and CA(151–231) reveal that the globular domain is composed of four helices and an extended amino-terminal strand. CA(146–231) dimerizes through parallel packing of helix 2 across a dyad. The MHR is distinct from the dimer interface and instead forms an intricate hydrogen-bonding network that interconnects strand 1 and helices 1 and 2. Alignment of the CA(146–231) 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.