ArticleImmunity2021
Structural basis for the constitutive activity and immunomodulatory properties of the Epstein-Barr virus-encoded G protein-coupled receptor BILF1.
Article in Immunity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Activation of cytomegalovirus-encoded G protein-coupled receptor UL33 by an innate N-terminal peptide.Communications biology · 2026Article
- Constitutive activity among orphan G protein-coupled receptors: Molecular mechanisms and pharmacological perspectives.Molecular pharmacology · 2026Review
- Structural analysis reveals that water molecules mediate self-activation of GPR99.Communications biology · 2026Article
- Epstein-Barr virus-associated tumors: commonalities in pathogenesis and the tumor immune microenvironment.Frontiers in immunology · 2026Review
- Structural basis for ligand promiscuity and high signaling activity of Kaposi's Sarcoma-associated Herpesvirus-encoded GPCR.Nature communications · 2025Article
- Constitutively active orphan G protein-coupled receptors through the lenses of cryo-electron microscopy.The Journal of biological chemistry · 2025Review
- Monoclonal Antibody 5F1 Modulates Formyl Peptide Receptor 1 Conformation for Transmembrane Signaling.FASEB bioAdvances · 2025Article
- Third intracellular loop of HCMV US28 is necessary for signaling and viral reactivation.Journal of virology · 2025Article
- Structural insights into KSHV-GPCR constitutive activation and CXCL1 chemokine recognition.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Presence of herpesviruses, parvoviruses, and polyomaviruses in sinonasal lymphoma.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2024Article
- A homotrimeric GPCR architecture of the human cytomegalovirus revealed by cryo-EM.Cell discovery · 2024Article
- Constitutive activation mechanism of a class C GPCR.Nature structural & molecular biology · 2024Article
- Structural insights into ligand recognition and selectivity of the human hydroxycarboxylic acid receptor HCAR2.Cell discovery · 2023Article
- Mechanism of activation and biased signaling in complement receptor C5aR1.Cell research · 2023Article
- Cryo-EM structure of G-protein-coupled receptor GPR17 in complex with inhibitory G protein.MedComm · 2022Article
- Viral G Protein-Coupled Receptors Encoded by β- and γ-Herpesviruses.Annual review of virology · 2022Review
- The Chemokine System in Oncogenic Pathways Driven by Viruses: Perspectives for Cancer Immunotherapy.Cancers · 2022Review
- Atypical structural snapshots of human cytomegalovirus GPCR interactions with host G proteins.Science advances · 2022Article
- Comparison of Transcriptomic Signatures between Monkeypox-Infected Monkey and Human Cell Lines.Journal of immunology research · 2022Article
- Epstein-Barr Virus-Encoded BILF1 Orthologues From Porcine Lymphotropic Herpesviruses Display Common Molecular Functionality.Frontiers in endocrinology · 2022Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
Epstein-Barr virus (EBV) encodes a G protein-coupled receptor (GPCR) termed BILF1 that is essential for EBV-mediated immunosuppression and oncogenesis. BILF1 couples with inhibitory G protein (Gi), the major intracellular signaling effector for human chemokine receptors, and exhibits constitutive signaling activity; the ligand(s) for BILF1 are unknown. We studied the origins of BILF1's constitutive activity through structure determination of BILF1 bound to the inhibitory G protein (Gi) heterotrimer. The 3.2-Å resolution cryo-electron microscopy structure revealed an extracellular loop within BILF1 that blocked the typical chemokine binding site, suggesting ligand-autonomous receptor activation. Rather, amino acid substitutions within BILF1 transmembrane regions at hallmark ligand-activated class A GPCR "microswitches" stabilized a constitutively active BILF1 conformation for Gi coupling in a ligand-independent fashion. Thus, the constitutive activity of BILF1 promotes immunosuppression and virulence independent of ligand availability, with implications for the function of GPCRs encoded by related viruses and for therapeutic targeting of EBV.
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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.