Structural basis for the constitutive activity and immunomodulatory properties of the Epstein-Barr virus-encoded G protein-coupled receptor BILF1
| العنوان: | Structural basis for the constitutive activity and immunomodulatory properties of the Epstein-Barr virus-encoded G protein-coupled receptor BILF1 |
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| المؤلفون: | Deepa Waghray, Mette M. Rosenkilde, Qianhui Qu, Christian Berg, Maša Mavri, K. Christopher Garcia, Shoji Maeda, Brian K. Kobilka, Naotaka Tsutsumi, Georgios Skiniotis, Maibritt S. Baggesen |
| المصدر: | Immunity, vol. 54, no. 7, pp. 1405-1416, 2021. Tsutsumi, N, Qu, Q, Mavri, M, Baggesen, M S, Maeda, S, Waghray, D, Berg, C, Kobilka, B K, Rosenkilde, M M, Skiniotis, G & Garcia, K C 2021, ' Structural basis for the constitutive activity and immunomodulatory properties of the Epstein-Barr virus-encoded G protein-coupled receptor BILF1 ', Immunity, vol. 54, no. 7, pp. 1405-+ . https://doi.org/10.1016/j.immuni.2021.06.001 Immunity |
| بيانات النشر: | Elsevier BV, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Epstein-Barr Virus Infections, Herpesvirus 4, Human, HIGH-LEVEL EXPRESSION, ligand-indpendent signaling, receptor, Receptors, G-Protein-Coupled, ACTIVATION, Chemokine receptor, GPCR, 0302 clinical medicine, Sf9 Cells, Immunology and Allergy, Receptor, Effector, Ligand (biochemistry), viral GPCR, Transmembrane protein, Cell biology, BINDING-SITE, Infectious Diseases, CLASS-I MOLECULES, 030220 oncology & carcinogenesis, Chemokines, signaling, Protein Binding, Signal Transduction, LIGAND RECOGNITION, G protein, Immunology, Biology, Article, Cell Line, Viral Proteins, 03 medical and health sciences, Animals, Humans, Immunologic Factors, Epstein-Barr virus, G protein-coupled receptor, immune evasion, Binding Sites, COMPLEX, IDENTIFICATION, Cryoelectron Microscopy, CHEMOKINE, HEK293 Cells, 030104 developmental biology, Chemokine binding, VISUALIZATION, cryo-EM, SYSTEM, udc:636.09:616.9:578 |
| الوصف: | 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-angstrom 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. |
| وصف الملف: | application/pdf; text/url |
| تدمد: | 1074-7613 1097-4180 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4a7d6feb0c2fee0fe07b6eb0430e9d82 https://doi.org/10.1016/j.immuni.2021.06.001 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....4a7d6feb0c2fee0fe07b6eb0430e9d82 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10747613 10974180 |
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