Figure 6. A model for the interactions of hparp486 with damaged DNA.
The overall shape and Dmax of hparp486 (A), zf-parp (B), 30Blunt DNA (C) and their complexes (D and E) have been experimentally determined by SAXS. The Dmax of 180Å (a 65Å increase) and asymmetric shape of the zf-parp-30Blunt complex is consistent with a single parp zinc finger interacting the blunt end (D). The hparp486-30Blunt complex is also elongated (E), but increases in size by 90Å (to 240Å). To account for both the change in profile of the P(r) function (Fig. 5 A, C) and greater Dmax,we model this with a conformational change that occurs in the Zn3-BRCT region of the protein. In contrast, when interacting with nicked DNA (F) or a 3’ extension region (G), hparp486 forms a more compact complex but a conformational change still needs to be taken into account to reach a Dmax of ~200Å. We propose that ultimately the conformational change that occurs during binding of DNA leads to activation of the PARP-1 enzymatic domain.