ArticleThe Journal of biological chemistry2016
An Intrinsically Disordered Motif Mediates Diverse Actions of Monomeric C-reactive Protein.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 63 citations in OpenAlex.
- Monomeric C-reactive Protein Exacerbates Neuronal Injury and Enhances Microglial Activation after Global Cerebral Ischemia in Mice.Molecular neurobiology · 2025Article
- Review
- Evaluating the CRP Interactome: Insights into Possible Novel Roles in Cellular Signaling and Tumorigenicity.Current issues in molecular biology · 2025Review
- A conformational change of C-reactive protein drives neutrophil extracellular trap formation in inflammation.BMC biology · 2025Article
- Mapping autoantibody targets of full-length C-reactive protein in systemic lupus erythematosus: importance for neutrophil function and classical complement activation.Frontiers in immunology · 2025Article
- Redefining CRP in tissue injury and repair: more than an acute pro-inflammatory mediator.Frontiers in immunology · 2025Review
- Resveratrol Activates Antioxidant Protective Mechanisms in Cellular Models of Alzheimer's Disease Inflammation.Antioxidants (Basel, Switzerland) · 2024Article
- C-reactive protein lowers the serum level of IL-17, but not TNF-α, and decreases the incidence of collagen-induced arthritis in mice.Frontiers in immunology · 2024Article
- Monomeric C-reactive protein is associated with severity and prognosis of decompensated hepatitis B cirrhosis.Frontiers in immunology · 2024Article
- Higher monomeric C-reactive protein levels are associated with premature coronary artery disease.Frontiers in immunology · 2024Article
- C-Reactive Protein: Pathophysiology, Diagnosis, False Test Results and a Novel Diagnostic Algorithm for Clinicians.Diseases (Basel, Switzerland) · 2023Review
- Monomeric C-Reactive Protein in Atherosclerotic Cardiovascular Disease: Advances and Perspectives.International journal of molecular sciences · 2023Review
- Serum CRP interacts with SPARC and regulate immune response in severe cases of COVID-19 infection.Frontiers in immunology · 2023Article
- Fueling the flames of colon cancer - does CRP play a direct pro-inflammatory role?Frontiers in immunology · 2023Article
- Regulation of Conformational Changes in C-reactive Protein Alters its Bioactivity.Cell biochemistry and biophysics · 2022Review
- Associations of C-reactive protein isoforms with systemic lupus erythematosus phenotypes and disease activity.Arthritis research & therapy · 2022Article
- Monomeric C-reactive protein level is associated with osteoarthritis.Experimental and therapeutic medicine · 2022Article
- Secretory quality control constrains functional selection-associated protein structure innovation.Communications biology · 2022Article
- C-Reactive Protein: Friend or Foe? Phylogeny From Heavy Metals to Modified Lipoproteins and SARS-CoV-2.Frontiers in cardiovascular medicine · 2022Review
- mCRP as a Biomarker of Adult-Onset Still's Disease: Quantification of mCRP by ELISA.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most proinflammatory actions of C-reactive protein (CRP) are only expressed following dissociation of its native pentameric assembly into monomeric form (mCRP). However, little is known about what underlies the greatly enhanced activities of mCRP. Here we show that a single sequence motif, i.e. cholesterol binding sequence (CBS; a.a. 35-47), is responsible for mediating the interactions of mCRP with diverse ligands. The binding of mCRP to lipoprotein component ApoB, to complement component C1q, to extracellular matrix components fibronectin and collagen, to blood coagulation component fibrinogen, and to membrane lipid component cholesterol, are all found to be markedly inhibited by the synthetic CBS peptide but not by other CRP sequences tested. Likewise, mutating CBS in mCRP also greatly impairs these interactions. Functional experiments further reveal that CBS peptide significantly reduces the effects of mCRP on activation of endothelial cells in vitro and on acute induction of IL-6 in mice. The potency and specificity of CBS are critically determined by the N-terminal residues Cys-36, Leu-37, and His-38; while the versatility of CBS appears to originate from its intrinsically disordered conformation polymorphism. Together, these data unexpectedly identify CBS as the major recognition site of mCRP and suggest that this motif may be exploited to tune the proinflammatory actions of mCRP.
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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.