ArticleProceedings of the National Academy of Sciences of the United States of America2024
Structural basis for surface activation of the classical complement cascade by the short pentraxin C-reactive protein.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Exosome-derived biomarkers as non-invasive tools in stroke, Parkinson's disease, and Alzheimer's disease.Metabolic brain disease · 2026Review
- Bifunctional glycolipids targeting TLR4·MD-2 and short pentraxins.RSC chemical biology · 2026Article
- Significant correlations between blood lipids, cytokines, and C-reactive protein in healthy humans.Lipids in health and disease · 2026Article
- Advantages and Limitations of AlphaFold in Structural Biology: Insights from Recent Studies.The protein journal · 2026Review
- C-Reactive Protein and Neurological Autoimmune Diseases: Bridging the Diagnostic and Pathogenic Gap.International journal of molecular sciences · 2026Review
- Pathogen Evasion of Humoral Innate Immunity: Coping with C-Reactive Protein and Serum Amyloid A.International journal of molecular sciences · 2026Review
- Perioperative Blood Biomarkers of Infectious and Non-Infectious Postoperative Pulmonary Complications: A Narrative Review.Journal of clinical medicine · 2026Review
- Complement Components C1r and C8 Serve as Potential Inflammatory Biomarkers for Coronary Heart Disease Severity: The Mediating Role of C-Reactive Protein.Journal of inflammation research · 2026Article
- Elevated admission C-reactive protein identifies complicated or high-risk acute Stanford type B aortic dissection.Frontiers in immunology · 2026Observational
- Blood Marker-Based Machine Learning Model for Survival Prediction in Patients with Pneumoconiosis: Construction and External Validation.Journal of inflammation research · 2026Article
- Immunological and Inflammatory Characteristics of Severe Cutaneous Adverse Drug Reactions: A Retrospective Study.International journal of general medicine · 2026Article
- Evaluating the CRP Interactome: Insights into Possible Novel Roles in Cellular Signaling and Tumorigenicity.Current issues in molecular biology · 2025Review
- Encapsulants Affect Liposome Surface Interactions with Biological Systems.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Association of Complement Proteins with C Reactive Protein in Non-Obese Women with and Without Polycystic Ovary Syndrome.International journal of molecular sciences · 2025Article
- Redefining CRP in tissue injury and repair: more than an acute pro-inflammatory mediator.Frontiers in immunology · 2025Review
- C-reactive protein: the nexus between inflammation and protein misfolding diseases.Frontiers in immunology · 2025Review
- Selection and characterization of a peptide-based complement modulator targeting C1 of the innate immune system.RSC chemical biology · 2024Article
- C-reactive protein: structure, function, regulation, and role in clinical diseases.Frontiers in immunology · 2024Review
- Efficient expression and purification of rat CRP inFrontiers in immunology · 2024Article
- Risk Factors for Infusion Reactions Associated With Rituximab Therapy.Cancer diagnosis & prognosisArticle
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Authors and funding
10 authors.
Funding
Abstract
Human C-reactive protein (CRP) is a pentameric complex involved in immune defense and regulation of autoimmunity. CRP is also a therapeutic target, with both administration and depletion of serum CRP being pursued as a possible treatment for autoimmune and cardiovascular diseases, among others. CRP binds to phosphocholine (PC) moieties on membranes to activate the complement system via the C1 complex, but it is unknown how CRP, or any pentraxin, binds to C1. Here, we present a cryoelectron tomography (cryoET)-derived structure of CRP bound to PC ligands and the C1 complex. To gain control of CRP binding, a synthetic mimotope of PC was synthesized and used to decorate cell-mimetic liposome surfaces. Structure-guided mutagenesis of CRP yielded a fully active complex able to bind PC-coated liposomes that was ideal for cryoET and subtomogram averaging. In contrast to antibodies, which form Fc-mediated hexameric platforms to bind and activate the C1 complex, CRP formed rectangular platforms assembled from four laterally associated CRP pentamers that bind only four of the six available globular C1 head groups. Potential residues mediating lateral association of CRP were identified from interactions between unit cells in existing crystal structures, which rationalized previously unexplained mutagenesis data regarding CRP-mediated complement activation. The structure also enabled interpretation of existing biochemical data regarding interactions mediating C1 binding and identified additional residues for further mutagenesis studies. These structural data therefore provide a possible mechanism for regulation of complement by CRP, which limits complement progression and has consequences for how the innate immune system influences autoimmunity.
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