Refined solution structure of the dimeric N-terminal HHCC domain of HIV-2 integrase

The solution structure of the dimeric N-terminal domain of HIV-2 integrase (residues 1-55, named IN1-55) has been determined using NMR spectroscopy. T he structure of the monomer, which was already reported previously [Eijkele nboom et al. (1997) Curr. Biol., 7, 739-746], consists of four alpha -helic es and is well defined. Helices alpha1, alpha2 and alpha3 form a three-heli x bundle that is stabilized by zinc binding to His12, His16, Cys40 and Cys4 3. The dimer interface is formed by the N-terminal tail and the first half of helix alpha3. The orientation of the two monomeric units with respect to each other shows considerable variation. N-15 relaxation studies have been used to characterize the nature of the intermonomeric disorder. Comparison of the dimer interface with that of the well-defined dimer interface of HI V-1 IN1-55 shows that the latter is stabilized by additional hydrophobic in teractions and a potential salt bridge. Similar interactions cannot be form ed in HIV-2 IN1-55 [Cai et al. (1997) Nat. Struct. Biol., 4, 567-577], wher e the corresponding residues are positively charged and neutral ones.