Crystal structure of a Flp recombinase-Holliday junction complex: Assembly of an active oligomer by helix swapping

The crystal structure of a Flp recombinase tetramer bound to a Holliday junction intermediate has been determined at 2.65 Angstrom resolution. Only one of Flp's two domains, containing the active site, is structurally related to other lambda integrase family site-specific recombinases, such as Ore. The Flp active site differs, however, in that the helix containing the nucleophilic tyrosine is domain swapped, such that it cuts its DNA target in trans. The Flp tetramer displays pseudo fourfold symmetry matching that of the square planar Holliday junction substrate. This tetramer is stabilized by additional novel trans interactions among monomers. The structure illustrates how mechanistic unity is maintained on a chemical level while allowing for substantial variation on the structural level within a family of enzymes.