C5aR1 (C5a receptor 1), also known as CD88. is a G protein-coupled receptor (GPCR) that plays a central role in the innate immune system by mediating responses to the complement activation fragment C5a. As part of the complement cascade, C5a is a potent anaphylatoxin generated during inflammation, infections, or tissue injury. C5aR1 is expressed on myeloid cells (e.g., neutrophils, macrophages) and non-myeloid cells (e.g., endothelial cells, neurons), where it regulates chemotaxis, cytokine release, and phagocytosis. Its signaling contributes to both protective immunity and pathological inflammation, making it a therapeutic target in diseases like sepsis, autoimmune disorders, and chronic inflammatory conditions.
Recombinant C5aR1 proteins are engineered versions of the receptor, typically produced in heterologous expression systems such as mammalian cells (e.g., CHO or HEK293) or insect cells. These systems enable post-translational modifications critical for receptor folding and ligand binding. The recombinant protein often includes tags (e.g., FLAG, His-tag) for purification and detection. Structural studies using recombinant C5aR1 have revealed its seven-transmembrane domain architecture and dynamic interactions with C5a, aiding in the design of antagonists to block excessive inflammation.
Research applications of recombinant C5aR1 include ligand-receptor interaction assays, high-throughput drug screening, and mechanistic studies of inflammatory pathways. Dysregulation of C5a-C5aR1 signaling is implicated in conditions like rheumatoid arthritis, Alzheimer’s disease, and COVID-19-related hyperinflammation, driving interest in developing biologics or small molecules targeting this receptor. Recent advances in cryo-EM and X-ray crystallography using recombinant C5aR1 have further elucidated its activation mechanisms, providing a framework for structure-based drug discovery.
以下是关于C4c重组蛋白的参考文献示例(注：以下文献信息为假设性举例，可能非真实存在)：
1. **文献名称**：*Expression and functional characterization of recombinant human C4c in inflammatory regulation*
**作者**：Zhang Y, et al.
**摘要**：研究通过哺乳动物表达系统成功制备重组C4c蛋白，证实其在体外抑制补体过度激活，减少炎症因子释放，为治疗补体相关疾病提供潜在策略。
2. **文献名称**：*Structural analysis of C4c fragment using recombinant protein technology*
**作者**：Müller R, et al.
**摘要**：利用重组C4c蛋白进行晶体结构解析，揭示了其与补体调控蛋白C3b的结合位点，阐明了其在补体级联反应中的分子机制。
3. **文献名称**：*Recombinant C4c as a diagnostic marker for systemic lupus erythematosus*
**作者**：Chen L, et al.
**摘要**：开发基于重组C4c的ELISA检测方法，发现其在SLE患者血清中水平显著升高，提示C4c可作为疾病活动性的生物标志物。
4. **文献名称**：*Engineering recombinant C4c with enhanced stability for therapeutic applications*
**作者**：Kim H, et al.
**摘要**：通过定点突变改良重组C4c的热稳定性，证明其在动物模型中延长半衰期并有效缓解补体介导的组织损伤。
(注：实际研究中请通过学术数据库核实具体文献。)
C4c recombinant protein is derived from the complement component C4. a critical player in the immune system's complement cascade. The complement system, a cornerstone of innate immunity, comprises proteins that orchestrate pathogen clearance, inflammation, and tissue homeostasis. C4. a central component, participates in both the classical and lectin pathways. Upon activation, C4 is cleaved into C4a (an anaphylatoxin) and C4b, which binds pathogens or immune complexes. Further degradation of C4b generates C4c and C4d, with C4c retaining portions of the α and β chains of the parent molecule.
Recombinant C4c is produced using biotechnological methods, typically through expression in mammalian or bacterial systems followed by purification. Its production enables detailed study of complement activation dynamics, as C4c serves as a stable marker of classical/lectin pathway activity. Clinically, C4c has gained attention in autoimmune diseases like systemic lupus erythematosus (SLE), where chronic complement activation depletes C4 levels. Measuring C4c, rather than total C4. may better reflect disease activity, as it avoids confounding factors like genetic C4 deficiencies.
In research, recombinant C4c aids in elucidating structural-functional relationships within the complement system, including interactions with regulators (e.g., complement factor I) or receptors. It also holds therapeutic potential, such as in designing inhibitors to modulate excessive complement activation in conditions like autoimmune disorders or ischemia-reperfusion injury. Furthermore, recombinant C4c serves as an antigen in diagnostic assays to detect complement-related pathologies.
Overall, C4c recombinant protein bridges basic immunology and translational medicine, offering tools to decode complement mechanisms and develop targeted therapies. Its study underscores the interplay between immune regulation and disease, highlighting opportunities for precision medicine in complement-driven disorders.
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