Structure of the Amino-Terminal Core Domain of the HIV-1 Capsid Protein

Abstract

The three-dimensional structure of the amino-terminal core domain (residues 1 through 151) of the human immunodeficiency virus-type 1 (HIV-1) capsid protein has been solved by multidimensional heteronuclear magnetic resonance spectroscopy. The structure is unlike those of previously characterized viral coat proteins and is composed of seven α helices, two β hairpins, and an exposed partially ordered loop. The domain is shaped like an arrowhead, with the β hairpins and loop exposed at the trailing edge and the carboxyl-terminal helix projecting from the tip. The proline residue Pro¹ forms a salt bridge with a conserved, buried aspartate residue (Asp⁵¹), which suggests that the amino terminus of the protein rearranges upon proteolytic maturation. The binding site for cyclophilin A, a cellular rotamase that is packaged into the HIV-1 virion, is located on the exposed loop and encompasses the essential proline residue Pro⁹⁰. In the free monomeric domain, Pro⁹⁰ adopts kinetically trapped cis and trans conformations, raising the possibility that cyclophilin A catalyzes interconversion of the cis- and trans-Pro⁹⁰ loop structures.