CRYSTAL STRUCTURE OF THE YEAST CELL-CYCLE CONTROL PROTEIN, P13^suc1, IN A STRAND-EXCHANGED DIMER. N. Khazanovich¹, K. S. Bateman¹, M. Chernaia¹, M. Michalak², M. N. G. James¹, ¹MRC Group in Protein Structure and Function, ²Cardiovascular Disease Research Group, Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada TOG 2H7

P13^suc1 from S. pombe is a member of the CDC28 kinase specific (CKS) class of cell-cycle control proteins, that includes CKS1 from S. cerevisiae and the human homologues CksHs1 and CksHs2. P13^suc1 participates in the regulation of p34^cdc2, a cyclin-dependent kinase controlling the G₁-S and the G₂-M transitions of the cell cycle. The CKS proteins are believed to exert their regulatory activity by binding to the kinase, in which case their function may be governed by their conformation or oligomerization state. Analysis of various assemblies of the CKS proteins, as found in different crystal forms, should help to clarify their role in cell cycle control. Previously determined X-ray structures of pl3^sucl, Ckshs1 and CksHs2 show that these proteins share a common fold but adopt different oligomeric states. P13^suc1 and CksHs1 were solved as monomers [1,2]. In addition, CksHs2 and pl3^suc1 were observed in assemblies of strand-exchanged dimers [3,4].

We report the X-ray crystal structure of pl3^suc1 to 1.95 Å resolution in space group C222₁. It is present in the crystals as a strand-exchanged dimer. The overall monomeric fold is preserved in each lobe of the dimer but a single [[beta]]-strand (Ile94 to Asp1O2) is exchanged between the central [[beta]]-sheets of each molecule.

Strand exchange, which has been observed for pl3^sucl in two different space groups, and for CksHs2, is now confirmed to bc an intrinsic feature of the CKS family. A switch between levels of assembly may serve to coordinate the function of the CKS proteins in cell cycle control.

1. Endicott, J. A., et al. EMBO J. 14, 1004 (1995).

2. Arvai, A. S., et al. J. Mol. Biol. 249, 835 (1995).

3. Parge, H. E., et al. Science 262, 387 (1993).

4. Bourne, Y., et al. Proc. Natl. Acad. Sci. USA 92, 10232 (1995).