STRUCTURE OF THE BACTERIOPHAGE-MU TRANSPOSASE CORE - A COMMON STRUCTURAL MOTIF FOR DNA TRANSPOSITION AND RETROVIRAL INTEGRATION

The crystal structure of the core domain of bacteriophage Mu transposase, MuA, has been determined at 2.4 Angstrom resolution. The first of two subdomains contains the active site and, despite very limited sequence homology, exhibits a striking similarity to the core domain of HIV-1 integrase, which carries out a similar set of biochemical reactions. It also exhibits more limited similarity to other nucleases, RNase fl and RuvC. The second, a beta barrel, connects to the first subdomain through several contacts. Three independent determinations of the monomer structure from two crystal forms all show the active site held in a similar, apparently inactive configuration. The enzymatic activity of MuA is known to be activated by formation of a DNA-bound tetramer of the protein. We propose that the connections between the two subdomains may be involved in the cross-talk between the active site and the other domains of the transposase that controls the activity of the protein.