Related Experiment Video
Updated: Jun 11, 2026
06:50
Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions
Published on: January 26, 2024
SH2 domains recognize contextual peptide sequence information to determine selectivity
Bernard A Liu1, Karl Jablonowski, Eshana E Shah
1Ben May Department for Cancer Research and Committee on Cancer Biology, The University of Chicago, Chicago, Illinois 60637, USA.
Molecular & Cellular Proteomics : MCP
|July 15, 2010
Summary
Src homology 2 (SH2) domains exhibit remarkable selectivity in recognizing phosphotyrosine peptides. Their binding specificity is determined by local sequence context, including permissive and non-permissive amino acid residues.
Area of Science:
- Molecular Biology
- Biochemistry
- Cell Signaling
Background:
- Protein interaction domains, such as Src homology 2 (SH2) domains, are crucial for specificity in cellular signaling pathways.
- SH2 domains bind to phosphorylated tyrosine residues on proteins, mediating downstream signaling events initiated by tyrosine kinases.
- Understanding SH2 domain selectivity is fundamental to deciphering phosphotyrosine signaling networks.
Purpose of the Study:
- To investigate the selectivity of SH2 domains in recognizing diverse phosphotyrosine peptide ligands.
- To elucidate the mechanisms underlying SH2 domain binding specificity.
- To assess the impact of local sequence context on SH2 domain-ligand interactions.
Main Methods:
- Examined interactions between 50 different SH2 domains and 192 phosphotyrosine peptides.
- Peptides represented physiological motifs from FGF, insulin, and IGF-1 receptor pathways.
- Analyzed binding data to identify determinants of SH2 domain selectivity.
Main Results:
- Individual SH2 domains display distinct recognition properties and high selectivity for specific peptide motifs.
- Selectivity extends beyond previously known binding motifs, influenced by both enhancing and inhibitory neighboring amino acid residues.
- Local sequence context significantly impacts SH2 domain binding affinity and specificity.
Conclusions:
- SH2 domain selectivity is governed by a complex interplay of local amino acid residues surrounding the phosphotyrosine site.
- This contextual dependence increases the information content of peptide ligands, enabling precise molecular recognition.
- The findings provide a broader paradigm for ligand recognition by protein interaction domains in physiological signaling.
Related Concept Videos
02:26Conservation of Protein Domains Over Different Proteins
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
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...
02:40Ligand Binding Sites
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
01:25Selectins
Cell adhesion is an essential aspect of multicellularity. While stable cell interactions usually occur between cells of the same type, transient cell interactions occur between cells of different tissue types, such as between neutrophils and endothelial cells. Selectins are one class of cell adhesion molecules (CAMs) that bind carbohydrate ligands to form transient cell adhesion. They are rod-like proteins with a long extracellular part of variable length ending with the lectin domain, which...
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,...
01:25Dose-Response Relationship: Selectivity and Specificity
Drugs exert their therapeutic effects by interacting with receptors, enzymes, or ion channels that are present throughout the human body. The strength and duration of the interaction between a drug and its target receptor are characterized by the selectivity and specificity of the drug. Selectivity refers to a drug's strong preference for its intended target over other targets. For instance, isoprenaline, a non-selective β-adrenergic agonist, interacts with both β1- and β2-adrenergic receptors...