THE SOLUTION STRUCTURE AND DYNAMICS OF THE DNA-BINDING DOMAIN OF HMG-D FROM DROSOPHILA-MELANOGASTER

Background: The HMG-box is a conserved DNA-binding motif that has been identified in many high mobility group (HMG). proteins. HMG-D is a no n-histone chromosomal protein from Drosophila melanogaster that is clo sely related to the mammalian HMG-box proteins HMG-1 and HMG-2. Previo us structures determined for an HMG-box domain from rat and hamster ex hibit the same global topology, but differ significantly in detail. It has been suggested that these differences may arise from hinge motion s which allow the protein to adapt to the shape of its target DNA. Res ults: We present the solution structure of HMG-D determined by NMR spe ctroscopy to an overall precision of 0.85 angstrom root mean squared d eviation (rmsd) for the backbone atoms. The protein consists of an ext ended amino-terminal region and three alpha-helices that fold into a c haracteristic 'L' shape. The central core region of the molecule is hi ghly stable and maintains an angle of approximately 80-degrees between the axes of helices 2 and 3. The backbone dynamics determined from N- 15 NMR relaxation measurements show a high correlation with the mean r esidue rmsd determined from the calculated structures. Conclusions: Th e structure determined for the HMG-box motif from HMG-D is essentially identical to the structure determined for the B-domain of mammalian H MG-1. Since these proteins have significantly different sequences our results indicate that the global fold and the mode of interaction with DNA are also likely to be conserved in all eukaryotes.