3V7D

Crystal Structure of ScSkp1-ScCdc4-pSic1 peptide complex

Summary for 3V7D

• Entry DOI: 10.2210/pdb3v7d/pdb
• Related: 1NEX 3MKS
• Descriptor: Suppressor of kinetochore protein 1, Cell division control protein 4, Protein SIC1, ... (4 entities in total)
• Functional Keywords: wd 40 domain, phospho-peptide complex, e3 ubiquitin ligase, ligase, cell cycle, phospho binding protein, sic1, phosphorylation
• Biological source: Saccharomyces cerevisiae (Baker's yeast); More
• Total number of polymer chains: 5
• Total formula weight: 147054.61

Authors

Tang, X.,Orlicky, S.,Mittag, T.,Csizmok, V.,Pawson, T.,Forman-Kay, J.,Sicheri, F.,Tyers, M. (deposition date: 2011-12-20, release date: 2012-05-02, Last modification date: 2024-11-06)

Primary citation

Tang, X.,Orlicky, S.,Mittag, T.,Csizmok, V.,Pawson, T.,Forman-Kay, J.D.,Sicheri, F.,Tyers, M.
Composite low affinity interactions dictate recognition of the cyclin-dependent kinase inhibitor Sic1 by the SCFCdc4 ubiquitin ligase.
Proc.Natl.Acad.Sci.USA, 109:3287-3292, 2012

PubMed Abstract: The ubiquitin ligase SCF(Cdc4) (Skp1/Cul1/F-box protein) recognizes its substrate, the cyclin-dependent kinase inhibitor Sic1, in a multisite phosphorylation-dependent manner. Although short diphosphorylated peptides derived from Sic1 can bind to Cdc4 with high affinity, through systematic mutagenesis and quantitative biophysical analysis we show that individually weak, dispersed Sic1 phospho sites engage Cdc4 in a dynamic equilibrium. The affinities of individual phosphoepitopes serve to tune the overall phosphorylation site threshold needed for efficient recognition. Notably, phosphoepitope affinity for Cdc4 is dramatically weakened in the context of full-length Sic1, demonstrating the importance of regional environment on binding interactions. The multisite nature of the Sic1-Cdc4 interaction confers cooperative dependence on kinase activity for Sic1 recognition and ubiquitination under equilibrium reaction conditions. Composite dynamic interactions of low affinity sites may be a general mechanism to establish phosphorylation thresholds in biological responses.

PubMed: 22328159
DOI: 10.1073/pnas.1116455109

Experimental method

X-RAY DIFFRACTION (2.306 Å)