Structural basis of the activation of the CC chemokine receptor 5 by a chemokine agonist
| العنوان: | Structural basis of the activation of the CC chemokine receptor 5 by a chemokine agonist |
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| المؤلفون: | Isaikina, Polina, Tsai, Ching-Ju, Dietz, Nikolaus, Pamula, Filip, Grahl, Anne, Goldie, Kenneth N., Guixà-González, Ramon, Branco, Camila, Paolini-Bertrand, Marianne, Calo, Nicolas, Cerini, Fabrice, Schertler, Gebhard F. X., Hartley, Oliver, Stahlberg, Henning, Maier, Timm, Deupi, Xavier, Grzesiek, Stephan |
| المصدر: | Science Advances Science Advances, 7 (25) |
| بيانات النشر: | AMER ASSOC ADVANCEMENT SCIENCE |
| مصطلحات موضوعية: | Models, Molecular, Receptors, CCR5, Protein Conformation, Cryoelectron Microscopy, rantes, virus diseases, SciAdv r-articles, dynamics, Molecular Dynamics Simulation, inhibition, stomatognathic diseases, Structure-Activity Relationship, stomatognathic system, Structural Biology, parasitic diseases, potent, Humans, amino-terminus, recognition, human activities, Chemokine CCL5, Research Articles, Research Article, Signal Transduction |
| الوصف: | The human CC chemokine receptor 5 (CCR5) is a G protein–coupled receptor (GPCR) that plays a major role in inflammation and is involved in cancer, HIV, and COVID-19. Despite its importance as a drug target, the molecular activation mechanism of CCR5, i.e., how chemokine agonists transduce the activation signal through the receptor, is yet unknown. Here, we report the cryo-EM structure of wild-type CCR5 in an active conformation bound to the chemokine super-agonist [6P4]CCL5 and the heterotrimeric Gi protein. The structure provides the rationale for the sequence-activity relation of agonist and antagonist chemokines. The N terminus of agonist chemokines pushes onto specific structural motifs at the bottom of the orthosteric pocket that activate the canonical GPCR microswitch network. This activation mechanism differs substantially from other CC chemokine receptors that bind chemokines with shorter N termini in a shallow binding mode involving unique sequence signatures and a specialized activation mechanism. Science Advances, 7 (25) ISSN:2375-2548 |
| وصف الملف: | application/application/pdf; application/pdf |
| تدمد: | 2375-2548 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::301ea7bbac423c72673fd88af47f376dTest https://infoscience.epfl.ch/record/287388Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....301ea7bbac423c72673fd88af47f376d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23752548 |
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