ArticleProceedings of the National Academy of Sciences of the United States of America2024
Structural insights into KSHV-GPCR constitutive activation and CXCL1 chemokine recognition.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Molecular basis of CXC chemokine receptor 3 ligand multispecificity.Science advances · 2026Article
- Activation of cytomegalovirus-encoded G protein-coupled receptor UL33 by an innate N-terminal peptide.Communications biology · 2026Article
- Targeting of Kaposi's sarcoma-associated herpesvirus by immunotoxins directed against the viral G protein-coupled receptor, ORF74.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- G Protein-Coupled Receptors in Irritable Bowel Syndrome: Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Molecular insights into ligand recognition and signaling of OXGR1.Nature communications · 2025Article
- Human and viral chemokines differentially modulate G protein signaling, β-arrestin recruitment and chemotaxis mediated by the viral G protein-coupled receptor ORF74.Cell communication and signaling : CCS · 2025Article
- Structural basis for ligand promiscuity and high signaling activity of Kaposi's Sarcoma-associated Herpesvirus-encoded GPCR.Nature communications · 2025Article
- Monoclonal Antibody 5F1 Modulates Formyl Peptide Receptor 1 Conformation for Transmembrane Signaling.FASEB bioAdvances · 2025Article
- Encoding and decoding selectivity and promiscuity in the human chemokine-GPCR interaction network.Cell · 2025Article
- Deciphering complexity of GPCR signaling and modulation: implications and perspectives for drug discovery.Clinical science (London, England : 1979) · 2025Review
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Authors and funding
6 authors.
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Abstract
Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a viral G protein-coupled receptor, KSHV-GPCR, that contributes to KSHV immune evasion and pathogenesis of Kaposi's sarcoma. KSHV-GPCR shares a high similarity with CXC chemokine receptors CXCR2 and can be activated by selected chemokine ligands. Like other herpesvirus-encoded GPCRs, KSHV-GPCR is characterized by its constitutive activity by coupling to various G proteins. We investigated the structural basis of ligand-dependent and constitutive activation of KSHV-GPCR, obtaining high-resolution cryo-EM structures of KSHV-GPCR-Gi complexes with and without the bound CXCL1 chemokine. Analysis of the apo-KSHV-GPCR-Gi structure (2.81 Å) unraveled the involvement of extracellular loop 2 in constitutive activation of the receptor. In comparison, the CXCL1-bound KSHV-GPCR-Gi structure (3.01 Å) showed a two-site binding mode and provided detailed information of CXCL1 binding to a chemokine receptor. The dual activation mechanism employed by KSHV-GPCR represents an evolutionary adaptation for immune evasion and contributes to the pathogenesis of Kaposi's sarcoma. Together with results from functional assays that confirmed the structural models, these findings may help to develop therapeutic strategies for KSHV infection.
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