Is the function of the cdc2 kinase subunit proteins tuned by their propensities to oligomerize? Conformational states in solution of the cdc2 kinase partners p13(sucl) and p9(cksphy)

The cdc2 kinase subunit (cks) proteins play an essential function in the control of mitosis through their molecular complexes with the cdc2 kinase. In this work, we characterize the conformational state(s) in solution of the cks proteins p13(suc1) from Schizosaccharomyces pombe and p9(cksphy) from Physarum polycephalum. Monomers of p13(suc1) and p9(cksphy) were found to be markedly nonglobular, presumably with a long, nonfolded C-terminal moiety. This was in contrast to the previously published structure of p13(suc1), derived from crystallographic studies on a zinc-promoted p13(suc1) dimer, in which the individual p13(suc1) subunits had a globular conformation. This disparity was resolved when we found that the globular p13(suc1) fold undergoes a conformational transition into nonglobular monomers upon dissociation of the dimers following chelation of the zinc ions by ethylenediaminetetraacetic acid (EDTA). We also found that p13(suc1), but not p9(cksphy), forms stable dimers in the absence of metal ions. The topology of these EDTA-insensitive dimers likely resembles that of the human p9(ckshs2) protein, characterized by beta 4 strand exchange from each nonglobular monomer.