Crystal structure of NAD(+)-dependent DNA ligase: modular architecture andfunctional implications

DNA ligases catalyze the crucial step of joining the breaks in duplex DNA d uring DNA replication, repair and recombination, utilizing either ATP or NA D(+) as a cofactor. Despite the difference in cofactor specificity and limi ted overall sequence similarity, the two classes of DNA ligase share basica lly the same catalytic mechanism. In this study, the crystal structure of a n NAD (+) -dependent DNA ligase from Thermus filiformis, a 667 residue mult idomain protein, has been determined by the multiwavelength anomalous diffr action (MAD) method. It reveals highly modular architecture and a unique ci rcular arrangement of its four distinct domains. It also provides clues for protein flexibility and DIVA-binding sites. A model for the multidomain li gase action involving large conformational changes is proposed.