C5aR

Background

C5aR, also known as C5a receptor, is a ∼47 kDa glycoprotein receptor for C5a. Up to now, two C5a receptors have been cloned and identified, including C5AR1 (CD88) and C5AR2 (C5L2). These receptors are found on granulocytes, monocytes, mast cells, subsets of dendritic cells, as well as astrocytes and microglia. They are the member of the rhodopsin family of G-protein coupled receptors (GPCR) which contains a common structural motif of seven membrane-spanning domains linked together by three extracellular and three intracellular hydrophilic loops.

Acting as a complement receptor, C5aR is involved in the regulation of inflammatory responses, obesity, development, and cancers. C5AR signaling plays a key role in initiating neutrophil inflammation in immune complex (IC)-induced peritonitis. C5aR signaling initiates the inflammatory cascade by its effector effects on infiltrating and resident peritoneal cells, or by changing the balance between activation and inhibition of F on resident cells toward an inflammatory phenotype. C5AR signaling has been also shown to act as a key role in promoting tumor growth by regulating anti-tumor immunity. C5aR signaling can suppress the recruitment and function of CD4⁺ and CD8⁺ T cells in breast tumor-bearing mice. Besides, C5aR signaling is also involved in the generation of many inflammatory cytokines such as IL-8, IL-6, IL-17, and TNF-alpha, as well as a variety of leukocyte responses such as chemotaxis, homotypic aggregation, and upregulation of the number of CR1, CR3, and CR4 exposed on external membrane surfaces. C5aR has been considered as a promising therapeutic target for autoimmune and inflammatory disease syndromes due to its important role in mediating inflammatory responses.

Fig. 1 C5aR structure.Distributed under CC BY 3.0, from Wiki, without modification.

C5aR Functional Service

Creative Biolabs offers a broad spectrum of C5aR-related products, including C5aR inhibitors. These precisely developed tools are crucial for advancing research initiatives aimed at crafting therapeutic strategies for a wide variety of diseases.

Fig.2 The mechanism underlying the activation of C5aR1.¹

The complement system serves as a pivotal component of innate immunity, responding to pathogens with its effector, C5a. This molecule engages the C5aR1, triggering G protein and β-arrestin signaling pathways that regulate physiological responses. Aberrations in the C5a-C5aR1 axis are implicated in various inflammatory and immune disorders, yet understanding of its structural activation and signaling bias is incomplete. Researchers have delineated cryo-electron microscopy structures of the activated C5aR1–Gi protein complex, unveiling interactions with C5a, hexapeptidic agonist, and G protein-biased agonist. Through structural analyses, mutagenesis, and assays, researchers elucidate ligand recognition, bias signaling, and differing conformational dynamics, enhancing therapeutic design prospects.

Creative Biolabs offers a range of specialized services focused on C5aR, including comprehensive interaction analyses and supportive functional solutions, tailored to assist our valued clients in both scientific research and clinical applications.

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Reference

1. Feng, Yuying, et al. "Mechanism of activation and biased signaling in complement receptor C5aR1." Cell Research 33.4 (2023): 312-324. Distributed under Open Access license CC BY 4.0, without modification.