The integrase protein encoded by bacteriophage lambda (Int) catalyzes site a specific DNA recombination by which the viral chromosome is inserted into and excised out of the host genome through the formation of higher order recombinogenic nucleoprotein complexes. Genetic and biochemical studies on the Int carried out by isolating "multimer-specific" mutants had revealed informative functional characteristics of specific electrostatic interactions occurring among the functional domains of Int. The lambda Int recombination system shows the usefulness of structural and functional investigation of multimeric protein complexes through genetic studies on the electrostatic interactions of proteins comprising multimeric complexes. This approach is especially powerful when combined with NMR and X-ray crystallography results providing biological evidences of specific molecular interactions among proteins. (C) 2010 Elsevier Inc. All rights reserved.