THE X-RAY STRUCTURE OF THE DNA-BINDING DOMAIN FROM THE SACCHAROMYCES-CEREVISIAE CELL-CYCLE TRANSCRIPTION FACTOR MBP1 AT 2.1 ANGSTROM RESOLUTION

The structure of the DNA-binding domain of the Saccharomyces cerevisia e cell-cycle transcription factor Mbp1 has been solved using the multi -wavelength anomalous diffraction (MAD) technique on crystals of selen o-methionyl protein and refined at 2.1 Angstrom resolution. The molecu le is globular, consisting of a twisted, six-stranded beta-barrel that is packed against a loose bundle of four alpha-helices. Two of the be ta-strands in combination with two of the helices form a structure cha racteristic of the DNA-binding motif found in the CAP family of helix- turn-helix transcription factors. In Mbp1, this beta(2) alpha(2) motif is associated with regions of both positive electrostatic potential a nd sequence conservation within the Mbp1/Swi4 family, suggesting a rol e in DNA-binding in these proteins. A combination of structural and bi ochemical data further indicate a similarity to HNF3 gamma/fork head, a member of the family of ''winged'' helix-turn-helix proteins. We pro pose a model for DNA-binding involving a recognition helix in the majo r groove, phosphodiester backbone interactions through the beta-hairpi n and further base and/or phosphate interactions mediated by a C-termi nal, positively charged loop. (C) 1997 Academic Press Limited.