Viral GPCR US28 can signal in response to chemokine agonists of nearly unlimited structural degeneracy
| العنوان: | Viral GPCR US28 can signal in response to chemokine agonists of nearly unlimited structural degeneracy |
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| المؤلفون: | Olav Larsen, Jessica R. Ingram, Hidde L. Ploegh, Katja Spiess, John S Burg, K. Christopher Garcia, Timothy F Miles, Kevin Jude, Naotaka Tsutsumi, Gertrud Malene Hjortø, Deepa Waghray, Mette M. Rosenkilde |
| المصدر: | eLife, Vol 7 (2018) Miles, T F, Spiess, K, Jude, K M, Tsutsumi, N, Burg, J S, Ingram, J R, Waghray, D, Hjorto, G M, Larsen, O, Ploegh, H L, Rosenkilde, M M & Garcia, K C 2018, ' Viral GPCR US28 can signal in response to chemokine agonists of nearly unlimited structural degeneracy ', eLife, vol. 7, e35850 . https://doi.org/10.7554/eLife.35850 eLife |
| بيانات النشر: | eLife Sciences Publications Ltd, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Models, Molecular, 0301 basic medicine, Chemokine, yeast surface display, Protein Conformation, Structural Biology and Molecular Biophysics, S. cerevisiae, Cytomegalovirus, Ligands, Receptors, G-Protein-Coupled, membrane protein crystallography, Degeneracy (biology), Biology (General), biased signaling, biology, Chemistry, General Neuroscience, High-Throughput Nucleotide Sequencing, General Medicine, Ligand (biochemistry), 3. Good health, Peptide Conformation, Cell biology, Medicine, Receptors, Chemokine, Research Article, Human, Protein Binding, Signal Transduction, QH301-705.5, Science, Chemical biology, General Biochemistry, Genetics and Molecular Biology, Viral Proteins, 03 medical and health sciences, Biochemistry and Chemical Biology, GTP-Binding Proteins, Animals, Humans, G protein-coupled receptor, CX3CL1, General Immunology and Microbiology, Chemokine CX3CL1, chemokine, E. coli, HEK293 Cells, 030104 developmental biology, Structural biology, Mutation, biology.protein |
| الوصف: | Human cytomegalovirus has hijacked and evolved a human G-protein-coupled receptor into US28, which functions as a promiscuous chemokine 'sink’ to facilitate evasion of host immune responses. To probe the molecular basis of US28’s unique ligand cross-reactivity, we deep-sequenced CX3CL1 chemokine libraries selected on ‘molecular casts’ of the US28 active-state and find that US28 can engage thousands of distinct chemokine sequences, many of which elicit diverse signaling outcomes. The structure of a G-protein-biased CX3CL1-variant in complex with US28 revealed an entirely unique chemokine amino terminal peptide conformation and remodeled constellation of receptor-ligand interactions. Receptor signaling, however, is remarkably robust to mutational disruption of these interactions. Thus, US28 accommodates and functionally discriminates amongst highly degenerate chemokine sequences by sensing the steric bulk of the ligands, which distort both receptor extracellular loops and the walls of the ligand binding pocket to varying degrees, rather than requiring sequence-specific bonding chemistries for recognition and signaling. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::391346b1ad4e89207e3472bc3eb832d3 https://elifesciences.org/articles/35850 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....391346b1ad4e89207e3472bc3eb832d3 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |