CRYSTAL-STRUCTURE OF THE CELL CYCLE-REGULATORY PROTEIN SUC1 REVEALS ABETA-HINGE CONFORMATIONAL SWITCH

The Schizosaccharomyces pombe cell cycle-regulatory protein suc1, name d as the suppressor of cdc2 temperature-sensitive mutations, is essent ial for cell cycle progression. To understand suc1 structure-function relationships and to help resolve conflicting interpretations of suc1 function based on genetic studies of suc1 and its functional homologs in both lower and higher eukaryotes, we have determined the crystal st ructure of the beta-interchanged suc1 dimer, Each domain consists of t hree alpha-helices and a four-stranded beta-sheet, completed by the in terchange of terminal beta-strands between the two subunits, This beta -interchanged suc1 dimer, when compared with the beta-hairpin single-d omain folds of suc1, reveals a beta-hinge motif formed by the conserve d amino acid sequence HVPEPH. This beta-hinge mediates the subunit con formation and assembly of suc1: closing produces the intrasubunit beta -hairpin and single-domain fold, whereas opening leads to the intersub unit beta-strand interchange and interlocked dimer assembly reported h ere, This conformational switch markedly changes the surface accessibi lity of sequence-conserved residues available for recognition of cycli n-dependent kinase, suggesting a structural mechanism for beta-hinge-m ediated regulation of suc1 biological function. Thus, suc1 belongs to the family of domain-swapping proteins, consisting of intertwined and dimeric protein structures in which the dual assembly modes regulate t heir function.