Structural basis for chemokine recognition and activation of a viral G protein-coupled receptor
Chemokines are small proteins that function as immune modulators through activation of chemokine G protein–coupled receptors (GPCRs). Several viruses also encode chemokines and chemokine receptors to subvert the host immune response. How protein ligands activate GPCRs remains unknown. We report the...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
American Association for the Advancement of Science (AAAS)
2017
|
| Online Access: | http://hdl.handle.net/1721.1/107655 https://orcid.org/0000-0001-5923-3843 https://orcid.org/0000-0002-1090-6071 |
| _version_ | 1811095790126366720 |
|---|---|
| author | Burg, J. S. Ingram, J. R. Venkatakrishnan, A. J. Jude, K. M. Dukkipati, A. Feinberg, E. N. Waghray, D. Dror, R. O. Garcia, K. C. Angelini, Alessandro Ploegh, Hidde |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Burg, J. S. Ingram, J. R. Venkatakrishnan, A. J. Jude, K. M. Dukkipati, A. Feinberg, E. N. Waghray, D. Dror, R. O. Garcia, K. C. Angelini, Alessandro Ploegh, Hidde |
| author_sort | Burg, J. S. |
| collection | MIT |
| description | Chemokines are small proteins that function as immune modulators through activation of chemokine G protein–coupled receptors (GPCRs). Several viruses also encode chemokines and chemokine receptors to subvert the host immune response. How protein ligands activate GPCRs remains unknown. We report the crystal structure at 2.9 angstrom resolution of the human cytomegalovirus GPCR US28 in complex with the chemokine domain of human CX3CL1 (fractalkine). The globular body of CX3CL1 is perched on top of the US28 extracellular vestibule, whereas its amino terminus projects into the central core of US28. The transmembrane helices of US28 adopt an active-state–like conformation. Atomic-level simulations suggest that the agonist-independent activity of US28 may be due to an amino acid network evolved in the viral GPCR to destabilize the receptor’s inactive state. |
| first_indexed | 2024-09-23T16:28:01Z |
| format | Article |
| id | mit-1721.1/107655 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:28:01Z |
| publishDate | 2017 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1076552022-10-02T08:06:28Z Structural basis for chemokine recognition and activation of a viral G protein-coupled receptor Burg, J. S. Ingram, J. R. Venkatakrishnan, A. J. Jude, K. M. Dukkipati, A. Feinberg, E. N. Waghray, D. Dror, R. O. Garcia, K. C. Angelini, Alessandro Ploegh, Hidde Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Angelini, Alessandro Ploegh, Hidde Chemokines are small proteins that function as immune modulators through activation of chemokine G protein–coupled receptors (GPCRs). Several viruses also encode chemokines and chemokine receptors to subvert the host immune response. How protein ligands activate GPCRs remains unknown. We report the crystal structure at 2.9 angstrom resolution of the human cytomegalovirus GPCR US28 in complex with the chemokine domain of human CX3CL1 (fractalkine). The globular body of CX3CL1 is perched on top of the US28 extracellular vestibule, whereas its amino terminus projects into the central core of US28. The transmembrane helices of US28 adopt an active-state–like conformation. Atomic-level simulations suggest that the agonist-independent activity of US28 may be due to an amino acid network evolved in the viral GPCR to destabilize the receptor’s inactive state. Swiss National Science Foundation National Institutes of Health (U.S.) (Pioneer Award) Virginia and D.K. Ludwig Fund for Cancer Research 2017-03-22T19:40:55Z 2017-03-22T19:40:55Z 2014-12 2015-03 Article http://purl.org/eprint/type/JournalArticle 0036-8075 1095-9203 http://hdl.handle.net/1721.1/107655 Burg, J. S. et al. “Structural Basis for Chemokine Recognition and Activation of a Viral G Protein-Coupled Receptor.” Science 347.6226 (2015): 1113–1117. https://orcid.org/0000-0001-5923-3843 https://orcid.org/0000-0002-1090-6071 en_US http://dx.doi.org/10.1126/science.aaa5026 Science Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for the Advancement of Science (AAAS) PMC |
| spellingShingle | Burg, J. S. Ingram, J. R. Venkatakrishnan, A. J. Jude, K. M. Dukkipati, A. Feinberg, E. N. Waghray, D. Dror, R. O. Garcia, K. C. Angelini, Alessandro Ploegh, Hidde Structural basis for chemokine recognition and activation of a viral G protein-coupled receptor |
| title | Structural basis for chemokine recognition and activation of a viral G protein-coupled receptor |
| title_full | Structural basis for chemokine recognition and activation of a viral G protein-coupled receptor |
| title_fullStr | Structural basis for chemokine recognition and activation of a viral G protein-coupled receptor |
| title_full_unstemmed | Structural basis for chemokine recognition and activation of a viral G protein-coupled receptor |
| title_short | Structural basis for chemokine recognition and activation of a viral G protein-coupled receptor |
| title_sort | structural basis for chemokine recognition and activation of a viral g protein coupled receptor |
| url | http://hdl.handle.net/1721.1/107655 https://orcid.org/0000-0001-5923-3843 https://orcid.org/0000-0002-1090-6071 |
| work_keys_str_mv | AT burgjs structuralbasisforchemokinerecognitionandactivationofaviralgproteincoupledreceptor AT ingramjr structuralbasisforchemokinerecognitionandactivationofaviralgproteincoupledreceptor AT venkatakrishnanaj structuralbasisforchemokinerecognitionandactivationofaviralgproteincoupledreceptor AT judekm structuralbasisforchemokinerecognitionandactivationofaviralgproteincoupledreceptor AT dukkipatia structuralbasisforchemokinerecognitionandactivationofaviralgproteincoupledreceptor AT feinbergen structuralbasisforchemokinerecognitionandactivationofaviralgproteincoupledreceptor AT waghrayd structuralbasisforchemokinerecognitionandactivationofaviralgproteincoupledreceptor AT drorro structuralbasisforchemokinerecognitionandactivationofaviralgproteincoupledreceptor AT garciakc structuralbasisforchemokinerecognitionandactivationofaviralgproteincoupledreceptor AT angelinialessandro structuralbasisforchemokinerecognitionandactivationofaviralgproteincoupledreceptor AT ploeghhidde structuralbasisforchemokinerecognitionandactivationofaviralgproteincoupledreceptor |