Functional interactions of the HHCC domain of Moloney murine leukemia virus integrase revealed by nonoverlapping complementation and zinc-dependent dimerization

The retroviral integrase (IN) is required for the integration of viral DNA into the host genome. The N terminus of IN contains an HHCC zinc finger-lik e motif, which is conserved among all retroviruses. To study the function o f the HHCC domain of Moloney murine leukemia virus IN, the first N-terminal 105 residues were expressed independently. This HHCC domain protein is fou nd to complement a completely nonoverlapping construct lacking the HHCC dom ain for strand transfer, 3' processing and coordinated disintegration react ions, revealing trans interactions among IN domains. The HHCC domain protei n binds zinc at a 1:1 ratio and changes its conformation upon binding to zi nc. The presence of zinc within the HHCC domain stimulates selective integr ation processes. Zinc promotes the dimerization of the HHCC domain and prot ects it from N-ethylmaleimide modification. These studies dissect and defin e the requirement for the HHCC domain, the exact function of which remains unknown.