C3-dependent effector functions of complement
Alessandra Zarantonello1, Margot Revel1, Anne Grunenwald1
1Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Paris, France.
Insights
Complement component 3 (C3) is central to immune responses, mediating functions via fragments like C3a and C3b. This review details C3 forms, fragments, receptors, and their roles in health and disease.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- Complement component 3 (C3) is a key effector molecule in the complement system.
- C3 mediates diverse biological functions through specific binding sites and receptors.
Purpose of the Study:
- To provide a comprehensive overview of C3 forms, fragments, and their interactions with complement receptors.
- To highlight the role of C3 in human health and disease, including deficiencies and uncontrolled activation.
- To detail the structural aspects of C3 activation and fragment generation.
Main Methods:
- Review of existing literature on C3 structure, function, and interactions.
- Analysis of C3 fragment binding to complement receptors.
- Examination of cellular expression and functional diversity of C3 receptors.
Main Results:
- Detailed description of native C3, C3 [H2O], intracellular C3, and C3 fragments (C3a, C3b, iC3b, C3dg/C3d).
- Elucidation of C3a receptor interactions and opsonin (C3b, iC3b, C3dg/C3d) binding to complement receptors.
- Categorization of receptors into those with and without complement regulatory functions.
Conclusions:
- C3 activation fragments trigger diverse cellular processes crucial in both health and disease.
- Understanding C3-receptor interactions provides insights into immune system regulation and pathology.
- This review offers an updated analysis of C3-mediated cellular events and their implications.
Abstract:
C3 is the central effector molecule of the complement system, mediating its multiple functions through different binding sites and their corresponding receptors. We will introduce the C3 forms (native C3, C3 [H2 O], and intracellular C3), the C3 fragments C3a, C3b, iC3b, and C3dg/C3d, and the C3 expression sites. To highlight the important role that C3 plays in human biological processes, we will give an overview of the diseases linked to C3 deficiency and to uncontrolled C3 activation. Next, we will present a structural description of C3 activation and of the C3 fragments generated by complement regulation. We will proceed by describing the C3a interaction with the anaphylatoxin receptor, followed by the interactions of opsonins (C3b, iC3b, and C3dg/C3d) with complement receptors, divided into two groups: receptors bearing complement regulatory functions and the effector receptors without complement regulatory activity. We outline the molecular architecture of the receptors, their binding sites on the C3 activation fragments, the cells expressing them, the diversity of their functions, and recent advances. With this review, we aim to give an up-to-date analysis of the processes triggered by C3 activation fragments on different cell types in health and disease contexts.
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