Yang, Tingting, Li, Jian, Cheng, Xinyu, Lu, Qiuyuan, Farooq, Zara, Fu, Ying, Lv, Sijia, Nan, Weiwei, Yu, Boming, Duan, Jingjing et al (show 6 more authors)
(2024)
Structural analysis of the human C5a-C5aR1 complex using cryo-electron microscopy.
Journal of structural biology, 216 (3).
p. 108117.
ISSN 1047-8477, 1095-8657
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1-s2.0-S1047847724000571-main.pdf - Author Accepted Manuscript Available under License Creative Commons Attribution. Download (2MB) | Preview |
Abstract
The complement system is a complex network of proteins that plays a crucial role in the innate immune response. One important component of this system is the C5a-C5aR1 complex, which is critical in the recruitment and activation of immune cells. In-depth investigation of the activation mechanism as well as biased signaling of the C5a-C5aR1 system will facilitate the elucidation of C5a-mediated pathophysiology. In this study, we determined the structure of C5a-C5aR1-Gi complex at a high resolution of 3 Å using cryo-electron microscopy (Cryo-EM). Our results revealed the binding site of C5a, which consists of a polar recognition region on the extracellular side and an amphipathic pocket within the transmembrane domain. Furthermore, we found that C5a binding induces conformational changes of C5aR1, which subsequently leads to the activation of G protein signaling pathways. Notably, a key residue (M265) located on transmembrane helix 6 (TM6) was identified to play a crucial role in regulating the recruitment of β-arrestin driven by C5a. This study provides more information about the structure and function of the human C5a-C5aR1 complex, which is essential for the proper functioning of the complement system. The findings of this study can also provide a foundation for the design of new pharmaceuticals targeting this receptor with bias or specificity.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | G protein-coupled receptor (GPCR), C5aR1, Structure, Complement system, Cryo-electron microscopy |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 21 Aug 2024 09:27 |
| Last Modified: | 28 Feb 2026 01:33 |
| DOI: | 10.1016/j.jsb.2024.108117 |
| Related Websites: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3183966 |
| Disclaimer: | The University of Liverpool is not responsible for content contained on other websites from links within repository metadata. Please contact us if you notice anything that appears incorrect or inappropriate. |
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