SOLUTION STRUCTURE OF THE SEQUENCE-SPECIFIC HMG BOX OF THE LYMPHOCYTETRANSCRIPTIONAL ACTIVATOR SOX-4

Two groups of HMG box proteins are distinguished. Proteins in the firs t group contain multiple HMG boxes, are non-sequence-specific, and rec ognize structural features as found in cruciform DNA and cross-over DN A. The abundant chromosomal protein HMG-1 belongs to this subgroup. Pr oteins in the second group carry a single HMG box with affinity for th e minor groove of the heptamer motif AACAAAG or variations thereof. A solution structure for the non-sequence specific C-terminal HMG box of HMG-1 has recently been proposed. Now, we report the solution structu re of the sequence-specific HMG-box of the SRY-related protein Sox-4, NMR analysis demonstrated the presence of three alpha-helices (Val(10) -Gln(22), Glu(30)-Leu(41) and Phe(50)-Tyr(65)) connected by loop regio ns (Ser(23)-Ala(49) and Leu(42)-pro(49)). Helices I and II are positio ned in an antiparallel mode and form one arm of the HMG box. Helix III is less rigid, makes an average angle of about 90 degrees with helice s I and II, and constitutes the other arm of the molecule, As in HMG1B , the overall structure of the Sox-4 HMG box is L-shaped and is mainta ined by a cluster of conserved, mainly aromatic residues.