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-Structure paper
タイトル | Structural basis of the activation of the CC chemokine receptor 5 by a chemokine agonist. |
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ジャーナル・号・ページ | Sci Adv, Vol. 7, Issue 25, Year 2021 |
掲載日 | 2021年6月16日 |
著者 | Polina Isaikina / Ching-Ju Tsai / Nikolaus Dietz / Filip Pamula / Anne Grahl / Kenneth N Goldie / Ramon Guixà-González / Camila Branco / Marianne Paolini-Bertrand / Nicolas Calo / Fabrice Cerini / Gebhard F X Schertler / Oliver Hartley / Henning Stahlberg / Timm Maier / Xavier Deupi / Stephan Grzesiek / |
PubMed 要旨 | 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 ...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 G 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. |
リンク | Sci Adv / PubMed:34134983 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.15 Å |
構造データ | EMDB-12746, PDB-7o7f: |
由来 |
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キーワード | SIGNALING PROTEIN / G protein-coupled receptor (GPCR); CCR5; CCL5/RANTES; HIV entry; AIDS; membrane protein structure; / MEMBRANE PROTEIN |