ArticleProceedings of the National Academy of Sciences of the United States of America2012
Composite low affinity interactions dictate recognition of the cyclin-dependent kinase inhibitor Sic1 by the SCFCdc4 ubiquitin ligase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 58 citations in OpenAlex.
- SHARK-capture identifies functional motifs in intrinsically disordered protein regions.Protein science : a publication of the Protein Society · 2025Article
- SKP1-CUL1-F-box: Key molecular targets affecting disease progression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- N-WASP is competent for downstream signaling before full release from autoinhibition.The Journal of chemical physics · 2023Article
- Condensed-phase signaling can expand kinase specificity and respond to macromolecular crowding.Molecular cell · 2022Article
- Systematic Discovery of FBXW7-Binding Phosphodegrons Highlights Mitogen-Activated Protein Kinases as Important Regulators of Intracellular Protein Levels.International journal of molecular sciences · 2022Article
- The microprotein Nrs1 rewires the G1/S transcriptional machinery during nitrogen limitation in budding yeast.PLoS biology · 2022Article
- Counting Degrons: Lessons From Multivalent Substrates for Targeted Protein Degradation.Frontiers in physiology · 2022Review
- Intrinsically disordered proteins: modes of binding with emphasis on disordered domains.Open biology · 2021Review
- The diversity of molecular interactions involving intrinsically disordered proteins: A molecular modeling perspective.Computational and structural biotechnology journal · 2021Review
- Mechanisms of noncanonical binding dynamics in multivalent protein-protein interactions.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Proteome-wide signatures of function in highly diverged intrinsically disordered regions.eLife · 2019Article
- Systematic identification of phosphorylation-mediated protein interaction switches.PLoS computational biology · 2017Article
- An allosteric conduit facilitates dynamic multisite substrate recognition by the SCFNature communications · 2017Article
- TORC1 coordinates the conversion of Sic1 from a target to an inhibitor of cyclin-CDK-Cks1.Cell discovery · 2017Article
- A comparative study of the degradation of yeast cyclins Cln1 and Cln2.FEBS open bio · 2017Article
- Dynamic Protein Interaction Networks and New Structural Paradigms in Signaling.Chemical reviews · 2016Review
- The human Na(+)/H(+) exchanger 1 is a membrane scaffold protein for extracellular signal-regulated kinase 2.BMC biology · 2016Article
- Multiple Weak Linear Motifs Enhance Recruitment and Processivity in SPOP-Mediated Substrate Ubiquitination.Journal of molecular biology · 2016Article
- A Centromere-Signaling Network Underlies the Coordination among Mitotic Events.Trends in biochemical sciences · 2016Review
- Prb1 Protease Activity Is Required for Its Recognition by the F-Box Protein Saf1.Biochemistry · 2015Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.