High-throughput discovery and deep characterization of cyclin-CDK docking motifs
Mihkel Örd1,2, Matthew J Winters3, Mythili S Subbanna3
1University of Cambridge, CRUK Cambridge Institute, Cambridge, UK.
Biorxiv : the Preprint Server for Biology
|December 16, 2024
Summary
This study reveals new ways cyclins bind to their targets, uncovering a wider variety of cyclin docking motifs than previously known. These findings enhance our understanding of cell division regulation.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Cyclin-dependent kinases (CDKs) are crucial for cell division.
- Cyclin subunits control CDK specificity by binding to docking motifs in substrates.
Purpose of the Study:
- To map the binding interactions between human cyclins and peptide substrates.
- To identify novel cyclin docking motifs and understand their recognition mechanisms.
Main Methods:
- Quantitative intracellular binding assays.
- Large-scale tiled peptide screening of ~100,000 peptides against 11 human cyclins.
- Structural and saturation mutagenesis studies.
Main Results:
- Discovery of a broad repertoire of non-canonical cyclin docking motifs.
- Identification of distinct binding modes and sequence features governing motif recognition.
- Characterization of motif selectivity ranging from highly specific to pan-cyclin binders.
Conclusions:
- The findings reveal a more complex set of rules for cyclin-substrate interactions than previously understood.
- This work deepens our knowledge of how docking motifs fine-tune CDK activity and cell cycle progression.
- Provides a comprehensive resource for understanding cyclin specificity and affinity.
