Integrases encoded by fuselloviruses infecting hyperthermophilic archaea of the genus Sulfolobus are the archaeal members of the tyrosine recombinase family. These enzymes, known as SSV-type integrases (Int), catalyze viral integration into and excision from the specific sites on the host genome. SSV1 Int is the prototype of SSV-type integrases.

In a recent report in the Acta Crystallogr D Biol Crystallogr [1], Professor LIU Zhi-Jie’s lab at the Institute of Biophysics and Professor HUANG Li’s group at the Institute of Microbiology, Chinese Academy of Sciences have resolved the crystal structure of the C-terminal catalytic domain of SSV1 Int. This is the first structural study of an archaeal tyrosine recombinase. Structural comparison shows that the C-terminal domain of SSV1 Int possesses a core fold similar to those of tyrosine recombinases of both bacterial and eukaryal origins, except for the lack of a conserved helix corresponding to αI of Cre, indicating conservation of these enzymes among all three domains of life. Five of the six catalytic residues cluster around a basic cleft on the surface of the structure and the nucleophile Tyr314 is located on a flexible loop that stretches away from the central cleft, supporting the possibility that SSV1 Int cleaves the target DNA in a trans mode. Biochemical analysis suggests that the N-terminal domain is responsible for the dimerization of SSV1 Int. The C-terminal domain is capable of DNA cleavage and ligation, but at efficiencies significantly lower than those of the full-length protein. In addition, neither the N-terminal domain alone nor the C-terminal domain alone shows a strong sequence preference in DNA binding. Therefore, recognition of the core-type sequence and efficient catalysis by SSV1 Int presumably requires covalent linkage and interdomain communication between the two domains.

This work was supported by grants from the Ministry of Science and Technology of China, Natural Science Foundation of China and the Chinese Academy of Sciences.

[1] Zhan Z$, Ouyang S^$, Liang W, Zhang Z, Liu ZJ*, Huang L*. Structural and functional characterization of the C-terminal catalytic domain of the SSV1 integrase. Acta Cryst D68, 659-670. ($contributed equally)