HIN RECOMBINASE BOUND TO DNA - THE ORIGIN OF SPECIFICITY IN MAJOR ANDMINOR-GROOVE INTERACTIONS

The structure of the 52-amino acid DNA-binding domain of prokaryotic H in recombinase, complexed with a DNA recombination half-site, has been solved by x-ray crystallography at 2.3 angstrom resolution. The Hin d omain consists of a three-alpha-helix bundle, with the carboxyl-termin al helix inserted into the major groove of DNA, and two flanking exten ded polypeptide chains that contact bases in the minor groove. The ove rall structure displays features resembling both a prototypical bacter ial helix-turn-helix and the eukaryotic homeodomain, and in many respe cts is an intermediate between these two DNA-binding binding motifs. I n addition, a new structural motif is seen: the six-amino acid carboxy l-terminal peptide of the Hin domain runs along the minor groove at th e edge of the recombination site, with the peptide backbone facing the floor of the groove and side chains extending away toward the exterio r. The x-ray structure provides an almost complete explanation for DNA mutant binding studies in the Hin system and for DNA specificity obse rved in the Hin-related family of DNA invertases.