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Published on: May 7, 2018
The switches.ELM resource: a compendium of conditional regulatory interaction interfaces
Kim Van Roey1, Holger Dinkel, Robert J Weatheritt
1Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
Short linear motifs (SLiMs) regulate protein interactions and cell signaling. Over half of SLiMs are controlled by pre- or posttranslational switches, impacting protein function and molecular decisions.
Area of Science:
- Molecular Biology
- Cell Signaling
- Protein Interactions
Background:
- Short linear motifs (SLiMs) are crucial for protein interactions, controlling cellular processes.
- Context-dependent modulation of SLiMs impacts protein function and molecular decision-making in cell signaling.
Purpose of the Study:
- To identify and characterize pre- and posttranslational switch mechanisms regulating SLiM function.
- To curate SLiM-based switch mechanisms in the accessible switches.ELM resource.
- To analyze SLiMs for regulatory switch mechanisms and their prevalence.
Main Methods:
- Curation of experimentally validated SLiM-based switch mechanisms.
- Definition and integration of rules for analyzing SLiMs.
- Application of rules to known SLiMs to predict regulatory mechanisms.
Main Results:
- Identification of multiple pre- and posttranslational switch mechanisms for SLiMs.
- Evidence that over 50% of validated SLiMs are likely regulated by these switches.
- Enrichment of posttranslational modification sites near SLiMs, enabling integrated regulation.
Conclusions:
- SLiM regulation via switches is widespread and crucial for cell signaling.
- The switches.ELM resource provides a valuable tool for studying SLiM regulation.
- Understanding these mechanisms enhances knowledge of molecular regulation in cell signaling.
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