HIGH-RESOLUTION STRUCTURES OF VARIANT ZIF268-DNA COMPLEXES - IMPLICATIONS FOR UNDERSTANDING ZINC-FINGER DNA RECOGNITION

Background: Zinc fingers of the Cys(2)-His(2) Glass comprise one of th e largest families of eukaryotic DNA-binding motifs and recognize a di verse set of DNA sequences, These proteins have a relatively simple mo dular structure and key base contacts are typically made by a few resi dues from each finger. These features make the zinc finger motif an at tractive system for designing novel DNA-binding proteins and for explo ring fundamental principles of protein-DNA recognition, Results: Here we report the X-ray crystal structures of zinc finger-DNA complexes in volving three variants of Zif268, with multiple changes in the recogni tion helix of finger one. We describe the structure of each of these t hree-finger peptides bound to its corresponding target site. To help e lucidate the differential basis for site-specific recognition, the str uctures of four other complexes containing various combinations of the se peptides with alternative binding sites have also been determined, Conclusions: The protein-DNA contacts observed in these complexes reve al the basis for the specificity demonstrated by these Zif268 variants . Many, but not all, of the contacts can be rationalized in terms of a recognition code, but the predictive value of such a code is limited, The structures illustrate how modest changes in the docking arrangeme nt accommodate the new sidechain-base and sidechain-phosphate interact ions. Such adaptations help explain the versatility of naturally occur ring zinc finger proteins and their utility in design.