| Autor: |
Zhehua Shao, Yangxia Tan, Qingya Shen, Li Hou, Bingpeng Yao, Jiao Qin, Peiyu Xu, Chunyou Mao, Li-Nan Chen, Huibing Zhang, Dan-Dan Shen, Chao Zhang, Weijie Li, Xufei Du, Fei Li, Zhi-Hua Chen, Yi Jiang, H. Eric Xu, Songmin Ying, Honglei Ma, Yan Zhang, Huahao Shen |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Cell Discovery, Vol 8, Iss 1, Pp 1-11 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2056-5968 |
| DOI: |
10.1038/s41421-022-00403-4 |
| Popis: |
Abstract Chemokine receptors are a family of G-protein-coupled receptors with key roles in leukocyte migration and inflammatory responses. Here, we present cryo-electron microscopy structures of two human CC chemokine receptor–G-protein complexes: CCR2 bound to its endogenous ligand CCL2, and CCR3 in the apo state. The structure of the CCL2–CCR2–G-protein complex reveals that CCL2 inserts deeply into the extracellular half of the transmembrane domain, and forms substantial interactions with the receptor through the most N-terminal glutamine. Extensive hydrophobic and polar interactions are present between both two chemokine receptors and the Gα-protein, contributing to the constitutive activity of these receptors. Notably, complemented with functional experiments, the interactions around intracellular loop 2 of the receptors are found to be conserved and play a more critical role in G-protein activation than those around intracellular loop 3. Together, our findings provide structural insights into chemokine recognition and receptor activation, shedding lights on drug design targeting chemokine receptors. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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Full text from SpringerLink