Integrase (IN) is the retroviral enzyme responsible for the integration of the DNA copy of the retroviral genome into the host cellDNA. TheC-terminal domainof INis involved in DNA binding and enzyme multimerization. We previ-ously performed single amino acid substitutions in the C-terminal domain of the avian leukemia and sarcoma vir-uses (ALSV) IN [Moreauet al. (2002). Arch. , 1761–1778]. Here, we modelled these IN mutants and ana-lysed their ability tomediate concertedDNA integration (in anin vitroassay) as well as to formdimers (by size exclusion chromatography and protein–protein cross-linking). .