HOMOLOGY MODEL-BUILDING OF THE HMG-1 BOX STRUCTURAL DOMAIN

Nucleoproteins belonging to the HMG-1/-2 family possess homologous dom ains similar to 75 amino acids in length. These domains, termed HMG-1 boxes, are highly structured, compact, and mediate the interaction bet ween HMG-1 box-containing proteins and DNA in a variety of biological contexts. Homology model building experiments on HMG-1 box sequences ' threaded' through the H-1-NMR structure of an HMG-1 box from rat indic ate that the domain does not have rigid sequence requirements for its formation. Energy calculations indicate that the structure of all HMG- 1 box domains is stabilized primarily through hydrophobic interactions . We have found structural relationships in the absence of statistical ly significant sequence similarity, identifying several candidate prot eins which could possibly assume the same three-dimensional conformati on as the rat HMG-1 box motif. The threading technique provides a meth od by which significant structural similarities in a diverse protein f amily can be efficiently detected, and the 'structural alignment' deri ved by this method provides a rational basis through which phylogeneti c relationships and the precise sites of interaction between HMG-1 box proteins and DNA can be deduced.