ArticleCell2023
Molecular basis of anaphylatoxin binding, activation, and signaling bias at complement receptors.
Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- The association between serum antinuclear antibodies and premature ovarian insufficiency: a meta-analysis.Journal of ovarian research · 2025Pooled it
- Oral administration of ultrafine-grained Astragalus membranaceus enhances peripheral immunity in weaned black Xiangdong goats by upregulating the complement regulator C4bp and immunoglobulin responses.Molecular biology reports · 2026Article
- Molecular Determinants of G Protein Subtype-Specific Coupling to the Angiotensin II Type 1 Receptor.bioRxiv : the preprint server for biology · 2026Article
- Atypical signaling, ligand recognition and selective agonist discovery of complement receptor C5aR2.Cell research · 2026Article
- Molecular basis of diverse ligand recognition and species-specific pharmacology at the complement anaphylatoxin receptor C3aR.Nature communications · 2026Article
- Innate immunity: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- Docking of virtual libraries identifies small-molecule agonists of neurotensin receptors with analgesic activity.Nature communications · 2026Article
- Consumption of processed foods impairs memory function through dietary advanced glycation end-products.bioRxiv : the preprint server for biology · 2026Article
- Immune cell dynamics and cytokine regulation in cornea and transplantation.Frontiers in immunology · 2026Review
- The Role of the C3a-C3aR Pathway in Diseases: Latest Research Advances.Mediators of inflammation · 2026Review
- Complement tumor-crosstalk: the role of C5a receptors in urothelial carcinomas.Frontiers in immunology · 2026Review
- The Pleiotropic Effect of Complement C5a-C5aR1 Pathway in Diseases: From Immune Regulation to Targeted Therapy.International journal of molecular sciences · 2025Review
- The Concise Guide to PHARMACOLOGY 2025/26: G protein-coupled receptors.British journal of pharmacology · 2025Review
- A novel long-acting C5a-blocking cyclic peptide prevents sepsis-induced organ dysfunction via effective blockade of the inflammatory cascade.Signal transduction and targeted therapy · 2025Article
- PIONEER: A Periplasmic Display Platform for Synthetic Biology-Based Screening of Genetically Encoded Protein Regulators.bioRxiv : the preprint server for biology · 2025Article
- Emerging role of complement system in the induction of neuroinflammation in adenylosuccinate lyase deficiency disorder.Brain, behavior, & immunity - health · 2025Review
- Emerging roles for complement in lung transplantation.The Journal of clinical investigation · 2025Review
- A Novel Class of Complement 3a Receptor Agonists and Antagonists Derived from the TLQP-21 Peptide.Journal of medicinal chemistry · 2025Article
- A genetically encoded nanobody sensor reveals conformational diversity in β-arrestins orchestrated by distinct seven transmembrane receptors.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Single-cell profiling identifies hair cell SLC35F1 deficiency as a signature of primate cochlear aging.Nature aging · 2025Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 4 countries.
Funding
Abstract
The complement system is a critical part of our innate immune response, and the terminal products of this cascade, anaphylatoxins C3a and C5a, exert their physiological and pathophysiological responses primarily via two GPCRs, C3aR and C5aR1. However, the molecular mechanism of ligand recognition, activation, and signaling bias of these receptors remains mostly elusive. Here, we present nine cryo-EM structures of C3aR and C5aR1 activated by their natural and synthetic agonists, which reveal distinct binding pocket topologies of complement anaphylatoxins and provide key insights into receptor activation and transducer coupling. We also uncover the structural basis of a naturally occurring mechanism to dampen the inflammatory response of C5a via proteolytic cleavage of the terminal arginine and the G-protein signaling bias elicited by a peptide agonist of C3aR identified here. In summary, our study elucidates the innerworkings of the complement anaphylatoxin receptors and should facilitate structure-guided drug discovery to target these receptors in a spectrum of disorders.
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Registered trials
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.