THE HMG-1 BOX PROTEIN FAMILY - CLASSIFICATION AND FUNCTIONAL-RELATIONSHIPS

The abundant and highly-conserved nucleoproteins comprising the high m obility group-1/-2 (HMG-1/-2) family contains two homologous basic dom ains of about 75 amino acids, These basic domains, termed HMG-1 boxes, are highly structured and facilitate HMG-DNA interactions, Many prote ins that regulate various cellular functions involving DNA binding and whose target DNA sequences share common structural characteristics ha ve been identified as having an HMG-1 box; these proteins include the RNA polymerase I transcription factor UBF, the mammalian testis-determ ining factor SRY and the mitochondrial transcription factors ABF2 and mtTF1, among others, The sequences of 121 HMG-1 boxes have been compil ed and aligned in accordance with thermodynamic results from homology model building (threading) experiments, basing the alignment on struct ure rather than by using traditional sequence homology methods. The cl assification of a representative subset of these proteins was then det ermined using standard least-squares distance methods, The proteins se gregate into two groups, the first consisting of HMG-1/-2 proteins and the second consisting of proteins containing the HMG-1 box but which are not canonical HMG proteins, The proteins in the second group furth er segregate based on their function, their ability to bind specific s equences of DNA, or their ability to recognize discrete non-B-DNA stru ctures, The HMG-1 box provides an excellent example of how a specific protein motif, with slight alteration, can be used to recognize DNA in a variety of functional contexts.