ArticleNature communications2019
Structural insights into substrate recognition by the SOCS2 E3 ubiquitin ligase.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Methods to Study the Molecular Mechanism and Drive the Design of Protein Degraders.Chemical reviews · 2026Review
- Article
- SOCS2 inhibits the tumorigenesis of GISTs and increases the sensitivity of GISTs to imatinib by suppression of KIT activation.Scientific reports · 2025Article
- Proteolysis-targeting influenza vaccine strains induce broad-spectrum immunity and in vivo protection.Nature microbiology · 2025Article
- Leveraging Therapeutic Proteins and Peptides fromInternational journal of molecular sciences · 2024Article
- Article
- A Cullin 5-based complex serves as an essential modulator of ORF9b stability in SARS-CoV-2 replication.Signal transduction and targeted therapy · 2024Article
- Unravelling the druggability and immunological roles of the SOCS-family proteins.Frontiers in immunology · 2024Review
- Structure-based design of a phosphotyrosine-masked covalent ligand targeting the E3 ligase SOCS2.Nature communications · 2023Article
- Targeted Protein Degradation: Advances, Challenges, and Prospects for Computational Methods.Journal of chemical information and modeling · 2023Review
- HIV-Host Cell Interactions.Cells · 2023Review
- SOCS2 regulation of growth hormone signaling requires a canonical interaction with phosphotyrosine.Bioscience reports · 2022Article
- Emerging Roles of Non-proteolytic Ubiquitination in Tumorigenesis.Frontiers in cell and developmental biology · 2022Review
- Discovery of an exosite on the SOCS2-SH2 domain that enhances SH2 binding to phosphorylated ligands.Nature communications · 2021Article
- Cullin-5 (CUL5) as a potential prognostic marker in a pan-cancer analysis of human tumors.Bioengineered · 2021Article
- NEDD8 and ubiquitin ligation by cullin-RING E3 ligases.Current opinion in structural biology · 2021Review
- E3 Ligase Ligands for PROTACs: How They Were Found and How to Discover New Ones.SLAS discovery : advancing life sciences R & D · 2021Review
- Suppressor of Cytokine Signaling 2 Regulates Retinal Pigment Epithelium Metabolism by Enhancing Autophagy.Frontiers in neuroscience · 2021Article
- SOCS2 Suppresses Inflammation and Apoptosis during NASH Progression through Limiting NF-κB Activation in Macrophages.International journal of biological sciences · 2021Article
- Recent advances in synthetic and medicinal chemistry of phosphotyrosine and phosphonate-based phosphotyrosine analogues.RSC medicinal chemistry · 2020Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The suppressor of cytokine signaling 2 (SOCS2) acts as substrate recognition subunit of a Cullin5 E3 ubiquitin ligase complex. SOCS2 binds to phosphotyrosine-modified epitopes as degrons for ubiquitination and proteasomal degradation, yet the molecular basis of substrate recognition has remained elusive. Here, we report co-crystal structures of SOCS2-ElonginB-ElonginC in complex with phosphorylated peptides from substrates growth hormone receptor (GHR-pY595) and erythropoietin receptor (EpoR-pY426) at 1.98 Å and 2.69 Å, respectively. Both peptides bind in an extended conformation recapitulating the canonical SH2 domain-pY pose, but capture different conformations of the EF loop via specific hydrophobic interactions. The flexible BG loop is fully defined in the electron density, and does not contact the substrate degron directly. Cancer-associated SNPs located around the pY pocket weaken substrate-binding affinity in biophysical assays. Our findings reveal insights into substrate recognition and specificity by SOCS2, and provide a blueprint for small molecule ligand design.
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Registered trials
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.