STRUCTURAL CLASSIFICATION OF HTH DNA-BINDING DOMAINS AND PROTEIN-DNA INTERACTION MODES

This paper constitutes an attempt to rationalize the structural simila rities and differences that are observed among the HTH DNA-binding dom ains, and the various modes of protein-DNA interactions. It consists o f classifying all the domains of known structure into families on the basis of the spatial arrangement of their helices, irrespective of the type of loops and the presence of beta-strands, and examining the int eraction patterns between amino acids and DNA within each family. It i s found that the recognition helix and the preceding helix along the c hain have always the same relative orientation. Structural differences arise when considering three helices, corresponding usually to the re cognition helix and the two preceding ones, but sometimes to the recog nition helix and the two flanking helices. Using an automatic classifi cation procedure, seven main families are obtained, whose members have in common the spatial arrangement of their three key helices, but hav e sometimes different topology and belong to different species. The st ructural divergence among these families and the existence of structur al intermediates are analyzed. Searching these families systematically for recurrent motifs, leads to identify two specific turns, besides t he HTH turn. They both link the two helices preceding the recognition helix and are each characteristic of a given family. Furthermore, the conservation of protein-DNA interaction patterns is examined with resp ect to the structural alignments. These patterns are found to be relat ively well conserved within each family and to be different between th e different families. The agreement of the structural classification a nd the patterns of protein-DNA contacts justify our approach, and sugg ests its applicability, in particular for modelling protein-DNA intera ctions. (C) 1996 Academic Press Limited