CRYSTAL-STRUCTURE OF THE YEAST CELL-CYCLE CONTROL PROTEIN, P13(SUC1),IN A STRAND-EXCHANGED DIMER

Background: p13(suc1) from fission yeast is a member of the CDC28 kina se specific (CKS) class of cell-cycle control proteins, that includes CKS1 from budding yeast and the human homologues CksHs1 and CksHs2. p1 3(suc1) participates in the regulation of p34(cdc2), a cyclin-dependen t kinase controlling the G(1)-S and the G(2)-M transitions of the cell cycle. The CKS proteins are believed to exert their regulatory activi ty by binding to the kinase, in which case their function may be gover ned by their conformation or oligomerization state. Previously determi ned X-ray structures of p13(suc1), CksHs1 and CksHs2 show that these p roteins share a common fold but adopt different oligomeric states. Mon omeric forms of p13(suc1) and CksHs1 have been solved, In addition, Ck sHs2 and p13(suc1) have been observed by X-ray crystallography in asse mblies of strand-exchanged dimers, Analysis of various assemblies of t he CKS proteins, as found in different crystal forms, should help to c larify their role in cell-cycle control. Results: We report the X-ray crystal structure of p13(suc1) to 1.95 Angstrom resolution in space gr oup C222(1). It is present in the crystals as a strand-exchanged dimer . The overall monomeric fold is preserved in each lobe of the dimer bu t a single beta-strand (lle94-Asp102) is exchanged between the central beta-sheets of each molecule. Conclusions: Strand exchange, which has been observed for p13(suc1) in two different space groups, and for Ck sHs2, is now confirmed to be an intrinsic feature of the CKS family, A switch between levels of assembly may serve to coordinate the functio n of the CKS proteins in cell-cycle control.