ArticleScience signaling2010
Loops govern SH2 domain specificity by controlling access to binding pockets.
Article in Science signaling, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 152 citations in OpenAlex.
- Targeting the BMX in cancer: molecular mechanisms and emerging therapeutic strategies.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Efficient Isolation and Enrichment of SH2 Domain Protein Species from Plasma Exploiting Specific Peptide-Protein Interactions.ACS omega · 2025Article
- Update on Structure and Function of SH2 Domains: Mechanisms and Emerging Targeting Strategies.International journal of molecular sciences · 2025Review
- R2HaPpY: Rapid-robust phosphotyrosine peptide enrichment using HaloTag-Src SH2 pY superbinder.bioRxiv : the preprint server for biology · 2025Article
- STAP-1-derived peptide suppresses TCR-mediated T cell activation and ameliorates immune diseases by inhibiting STAP-1-LCK binding.ImmunoHorizons · 2025Article
- The structural influence of the oncogenic driver mutation N642H in the STAT5B SH2 domain.Protein science : a publication of the Protein Society · 2025Article
- The pathogenic T42A mutation in SHP2 rewires the interaction specificity of its N-terminal regulatory domain.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The pathogenic T42A mutation in SHP2 rewires the interaction specificity of its N-terminal regulatory domain.bioRxiv : the preprint server for biology · 2024Article
- Article
- Automated Enrichment of Phosphotyrosine Peptides for High-Throughput Proteomics.Journal of proteome research · 2023Article
- Article
- Synthesis and Biological Evaluation of 3-Amino-4,4-Dimethyl Lithocholic Acid Derivatives as Novel, Selective, and Cellularly Active Allosteric SHP1 Activators.Molecules (Basel, Switzerland) · 2023Article
- Automated Enrichment of Phosphotyrosine Peptides for High-Throughput Proteomics.bioRxiv : the preprint server for biology · 2023Article
- Engineering SH2 Domains with Tailored Specificities and Affinities.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Exploring the Binding Interaction Between Phosphotyrosine Peptides and SH2 Domains by Proximal Crosslinking.Methods in molecular biology (Clifton, N.J.) · 2023Article
- SH2 Domains: Folding, Binding and Therapeutical Approaches.International journal of molecular sciences · 2022Review
- Engineered SH2 Domains for Targeted Phosphoproteomics.ACS chemical biology · 2022Article
- Poxviruses and paramyxoviruses use a conserved mechanism of STAT1 antagonism to inhibit interferon signaling.Cell host & microbe · 2022Article
- Structural and biochemical analyses of selectivity determinants in chimeric Streptococcus Class A sortase enzymes.Protein science : a publication of the Protein Society · 2022Article
- A 200 nanoseconds all-atom simulation of the pH-dependent EF loop transition in bovine β-lactoglobulin. The role of the orientation of the E89 side chain.Journal of biomolecular structure & dynamics · 2022Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Cellular functions require specific protein-protein interactions that are often mediated by modular domains that use binding pockets to engage particular sequence motifs in their partners. Yet, how different members of a domain family select for distinct sequence motifs is not fully understood. The human genome encodes 120 Src homology 2 (SH2) domains (in 110 proteins), which mediate protein-protein interactions by binding to proteins with diverse phosphotyrosine (pTyr)-containing sequences. The structure of the SH2 domain of BRDG1 bound to a peptide revealed a binding pocket that was blocked by a loop residue in most other SH2 domains. Analysis of 63 SH2 domain structures suggested that the SH2 domains contain three binding pockets, which exhibit selectivity for the three positions after the pTyr in a peptide, and that SH2 domain loops defined the accessibility and shape of these pockets. Despite sequence variability in the loops, we identified conserved structural features in the loops of SH2 domains responsible for controlling access to these surface pockets. We engineered new loops in an SH2 domain that altered specificity as predicted. Thus, selective blockage of binding subsites or pockets by surface loops provides a molecular basis by which the diverse modes of ligand recognition by the SH2 domain may have evolved and provides a framework for engineering SH2 domains and designing SH2-specific inhibitors.
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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.