ArticleCommunications biology2020
Submolecular probing of the complement C5a receptor-ligand binding reveals a cooperative two-site binding mechanism.
Article in Communications biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 8 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
8 citing papers in PubMed, 16 citations in OpenAlex.
- UltrastrongScience advances · 2025Article
- Structural and Functional Effects of C5aR1 Antagonism in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy.Developmental neuroscience · 2025Article
- Biophysical investigations using atomic force microscopy can elucidate the link between mouthfeel and flavour perception.Nature food · 2024Review
- Revealing the signaling of complement receptors C3aR and C5aR1 by anaphylatoxins.Nature chemical biology · 2023Article
- Structural biology of complement receptors.Frontiers in immunology · 2023Review
- Emerging Approaches for the Management of Chemotherapy-Induced Peripheral Neuropathy (CIPN): Therapeutic Potential of the C5a/C5aR Axis.Pain and therapy · 2022Review
- In Vivo Pharmacodynamic Method to Assess Complement C5a Receptor Antagonist Efficacy.ACS pharmacology & translational science · 2022Article
- Emerging Role of C5 Complement Pathway in Peripheral Neuropathies: Current Treatments and Future Perspectives.Biomedicines · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
A current challenge to produce effective therapeutics is to accurately determine the location of the ligand-biding site and to characterize its properties. So far, the mechanisms underlying the functional activation of cell surface receptors by ligands with a complex binding mechanism remain poorly understood due to a lack of suitable nanoscopic methods to study them in their native environment. Here, we elucidated the ligand-binding mechanism of the human G protein-coupled C5a receptor (C5aR). We discovered for the first time a cooperativity between the two orthosteric binding sites. We found that the N-terminus C5aR serves as a kinetic trap, while the transmembrane domain acts as the functional site and both contributes to the overall high-affinity interaction. In particular, Asp282 plays a key role in ligand binding thermodynamics, as revealed by atomic force microscopy and steered molecular dynamics simulation. Our findings provide a new structural basis for the functional and mechanistic understanding of the GPCR family that binds large macromolecular ligands.
Indexed as
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What OpenQuestion holds
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.