Related Experiment Video
Updated: Aug 6, 2026
07:44
Identifying Protein-protein Interaction Sites Using Peptide Arrays
Published on: November 18, 2014
An Atlas of Short Linear Motif-Mediated Human Protein-Protein Interactions
Priyanka Madhu1, Caroline Benz1, Leandro Simonetti1
1Department of Chemistry for Life Sciences, Uppsala University, Husargatan 3, Box 576, 751 23 Uppsala, Sweden.
Biorxiv : the Preprint Server for Biology
|July 17, 2026
Summary
This study maps over 20,000 human protein-protein interactions mediated by short linear motifs (SLiMs) in disordered regions. The Atlas of SLiM-mediated Human protein-protein Interactions (ASHI) reveals novel binding activities and interaction mechanisms.
Area of Science:
- Proteomics
- Molecular Biology
- Bioinformatics
Background:
- Short linear motifs (SLiMs) in intrinsically disordered protein regions are vital for transient cellular interactions.
- The global interaction network of human SLiMs is largely unknown, hindering our understanding of cell physiology.
Purpose of the Study:
- To create a comprehensive map of human SLiM-mediated protein-protein interactions.
- To explore novel binding modes and activities of protein domains interacting with SLiMs.
- To investigate the mechanisms governing interaction specificity within disordered regions.
Main Methods:
- Screening over 800 human protein domains against a library of one million peptides.
- Utilizing high-throughput screening to identify SLiM-protein interactions.
- Developing the Atlas of SLiM-mediated Human protein-protein Interactions (ASHI) database.
Main Results:
- Mapped over 20,000 human protein-protein interactions involving SLiMs.
- Identified novel binding activities in enzymes, chaperones, RNA-binding proteins, and modification-reader domains.
- Revealed that disordered regions act as densely encoded interaction platforms with diverse specificity mechanisms.
Conclusions:
- The ASHI resource significantly expands the known SLiM interactome.
- Intrinsically disordered regions employ complex strategies for interaction specificity.
- This data provides a foundation for modeling dynamic networks, interpreting disease variants, and understanding the 'dark proteome'.
Related Concept Videos
02:04Protein-protein Interfaces
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a polypeptide...
02:04Protein-Protein Interfaces
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a polypeptide...
02:26Protein Networks
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
02:26Protein Networks
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
01:49Conserved Binding Sites
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
01:30Assembly of Signaling Complexes
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...