ArticleImmunology and cell biology2016
Discovery of functionally selective C5aR2 ligands: novel modulators of C5a signalling.
Article in Immunology and cell biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 80 citations in OpenAlex.
- Atypical signaling, ligand recognition and selective agonist discovery of complement receptor C5aR2.Cell research · 2026Article
- Complement 5a receptor 2 attenuates diabetic kidney disease by promoting mitochondria-associated endoplasmic reticulum membrane formation mediated by PSS-MFN2 interaction.Cell discovery · 2026Article
- High throughput mutational characterization of the GPCR ligand C5a using yeast display and deep sequencing.Structure (London, England : 1993) · 2026Article
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- Inhibition of terminal complement complex formation alleviates murine antibody-mediated TRALI.Blood · 2025Article
- Action of the Terminal Complement Pathway on Cell Membranes.The Journal of membrane biology · 2025Review
- A CD4Immunity · 2025Article
- Cell-intrinsic C5a synergizes with Dectin-1 in macrophages to mediate fungal killing.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Molecular insights into atypical modes of β-arrestin interaction with seven transmembrane receptors.Science (New York, N.Y.) · 2024Article
- Article
- Molecular basis of anaphylatoxin binding, activation, and signaling bias at complement receptors.Cell · 2023Article
- Therapeutic Potential of Targeting Complement C5a Receptors in Diabetic Kidney Disease.International journal of molecular sciences · 2023Review
- Structural biology of complement receptors.Frontiers in immunology · 2023Review
- TLQP-21 is a low potency partial C3aR activator on human primary macrophages.Frontiers in immunology · 2023Article
- Modulation of C5a-C5aR1 signaling alters the dynamics of AD progression.Journal of neuroinflammation · 2022Article
- Helix 8 in chemotactic receptors of the complement system.PLoS computational biology · 2022Article
- Complement C3b contributes toFrontiers in immunology · 2022Article
- Mitochondrial C5aR1 activity in macrophages controls IL-1β production underlying sterile inflammation.Science immunology · 2021Article
- Development of Synthetic Human and Mouse C5a: Application to Binding and Functional AssaysACS pharmacology & translational science · 2021Article
- Intrinsic bias at non-canonical, β-arrestin-coupled seven transmembrane receptors.Molecular cell · 2021Article
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
The complement cascade is comprised of a highly sophisticated network of innate immune proteins that are activated in response to invading pathogens or tissue injury. The complement activation peptide, C5a, binds two seven transmembrane receptors, namely the C5a receptor 1 (C5aR1) and C5a receptor 2 (C5aR2, or C5L2). C5aR2 is a non-G-protein-signalling receptor whose biological role remains controversial. Some of this controversy arises owing to the lack of selective ligands for C5aR2. In this study, a library of 61 peptides based on the C-terminus of C5a was assayed for the ability to selectively modulate C5aR2 function. Two ligands (P32 and P59) were identified as functionally selective C5aR2 ligands, exhibiting selective recruitment of β-arrestin 2 via C5aR2, partial inhibition of C5a-induced ERK1/2 activation and lipopolysaccharide-stimulated interleukin-6 release from human monocyte-derived macrophages. Importantly, neither ligand could induce ERK1/2 activation or inhibit C5a-induced ERK1/2 activation via C5aR1 directly. Finally, P32 inhibited C5a-mediated neutrophil mobilisation in wild-type, but not C5aR2(-/-) mice. These functionally selective ligands for C5aR2 are novel tools that can selectively modulate C5a activity in vitro and in vivo, and thus will be valuable tools to interrogate C5aR2 function.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.