ArticleNature communications2023
Insights into the ISG15 transfer cascade by the UBE1L activating enzyme.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 21 citations in OpenAlex.
- Understanding protein ISGylation, a multifaceted posttranslational modification.Cell chemical biology · 2026Review
- ISG15+ Müller glial subtype contributes to early blood-retinal barrier breakdown in diabetic retinopathy.The Journal of clinical investigation · 2026Article
- Steric Gating Contributes to the Preferential Ubiquitin Charging of BIRC6 by UBA6 versus UBA1.Nature communications · 2026Article
- USP5 acts as a proteolytic switch to control SDE2 function via UBL-directed cleavage.Nature communications · 2026Article
- Structural determinants for FAT10 activation and transfer from UBA6 to E2 enzymes.Nature communications · 2026Article
- Divergent pathogenic mechanisms of influenza A and influenza B viruses.Archives of microbiology · 2026Review
- UBE2L6 promotes invasion and metastasis of triple-negative breast cancer by enhancing autophagy through STK38 ISGylation.Cellular and molecular life sciences : CMLS · 2026Article
- The Emerging Role of Interferon-Stimulated Gene 15 (ISG15) in Pregnancy-Related Disorders.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- ISGylation is disrupted byiScience · 2026Article
- UBA6 specificity for ubiquitin E2 conjugating enzymes reveals a priority mechanism of BIRC6.Nature structural & molecular biology · 2026Article
- Cryo-EM structures of UBA6 reveal mechanisms of E1-E2 specificity and dual FAT10/ubiquitin thioester transfer.Nature communications · 2026Article
- Extracellular Lipopolysaccharide Triggers the Release of Unconjugated Interferon-Stimulated Gene 15 (ISG15) Protein from Macrophages via Type-I Interferon/Caspase-4/Gasdermin-D Pathway.Pathogens (Basel, Switzerland) · 2026Article
- Cryo-EM structures reveal the molecular mechanism of SUMO E1-E2 thioester transfer.Nature structural & molecular biology · 2025Article
- The ISGylation tapestry in cancer: weaving phenotypic plasticity through multidimensional regulatory looms.Cellular & molecular biology letters · 2025Review
- Interferon-induced protein ISG15 in the central nervous system, quo vadis?FEBS letters · 2025Review
- Unveiling the genetic biomarkers for ageing: evidence from a large sample genome-wide association study and in vivo validation.Journal of global health · 2025Article
- Molecular choreography of E1 enzymes in ubiquitin-like protein cascades: New insights into dynamics and specificity.The Journal of biological chemistry · 2025Review
- DIG-DUBs: mechanisms and functions of ISG15 deconjugation by human and viral cross-reactive ubiquitin proteases.Biochemical Society transactions · 2025Article
- ISG15-Dependent Stabilisation of USP18 Is Necessary but Not Sufficient to Regulate Type I Interferon Signalling in Humans.European journal of immunology · 2025Article
- Chemical Tools for Probing the Ub/Ubl Conjugation Cascades.Chembiochem : a European journal of chemical biology · 2025Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The attachment of the ubiquitin-like protein ISG15 to substrates by specific E1-E2-E3 enzymes is a well-established signalling mechanism of the innate immune response. Here, we present a 3.45 Å cryo-EM structure of a chemically trapped UBE1L-UBE2L6 complex bound to activated ISG15. This structure reveals the details of the first steps of ISG15 recognition and UBE2L6 recruitment by UBE1L (also known as UBA7). Taking advantage of viral effector proteins from severe acute respiratory coronavirus 2 (SARS-CoV-2) and influenza B virus (IBV), we validate the structure and confirm the importance of the ISG15 C-terminal ubiquitin-like domain in the adenylation reaction. Moreover, biochemical characterization of the UBE1L-ISG15 and UBE1L-UBE2L6 interactions enables the design of ISG15 and UBE2L6 mutants with altered selectively for the ISG15 and ubiquitin conjugation pathways. Together, our study helps to define the molecular basis of these interactions and the specificity determinants that ensure the fidelity of ISG15 signalling during the antiviral response.
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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.