Abstract
The mechanism of assembly of multiprotein complexes and the subsequent organization of activity are not well understood. Here we report the application of biophysical tools to investigate the relationship between structure and function in protein assemblies. We used as a model system the SCFSkp2 complex that targets p27Kip1 for ubiquitination and subsequent degradation; this process requires an adapter protein, Cks1. By dissecting the interactions between the different subunits we show that the properties of Cks1 are highly context dependent, and its activity is acquired only when the complex is fully assembled. The results provide insights into the central role of small adapters in macromolecular assembly and explain their high sequence conservation. Simultaneous and synergistic binding of multiple subunits in a complex provides the specificity and control required before the key cell-cycle regulator p27 is committed to degradation.
| Original language | English |
|---|---|
| Pages (from-to) | 718-724 |
| Number of pages | 7 |
| Journal | Nature Structural Biology |
| Volume | 10 |
| Issue number | 9 |
| DOIs | |
| State | Published - 1 Sep 2003 |
| Externally published | Yes |
Bibliographical note
Funding Information:We thank D. Vesprintsev for help with running the experiments, A. Hershko, M. Bycroft and S. Teichmann for helpful discussions, and B. Schulman and J. Endicott for providing clones. This work was supported by the Medical Research Council of the UK (MRC). L.S.I. was supported by a Career Development Award from the MRC, M.A.S. by an External Research Studentship from Trinity College, Cambridge, UK, and A.F. by a Human Frontier Science Program long-term fellowship.