Human C-reactive protein (CRP) is an acute phase protein made by the liver. CRP is a plasma protein that comes from the liver and is a member of the pentraxin family. It is an important element of any inflammatory reaction. CRP is homopentameric and Ca-binds phosphocholine (PCh). CRP expression is mostly controlled at the transcriptional level and, in the acute phase, interleukin 6 is the principal inducer of this gene. We have figured out the crystal structure of CRP and also the topology and chemical make-up of its ligand binding site. Inflammation, infection and tissue injury cause the largest boost in CRP levels. CRP can also be employed as a biomarker to allow doctors to track and monitor the activity of inflammatory conditions like rheumatoid arthritis, inflammatory bowel disease, cardiovascular disease etc.
CRP is very sensitive to infection, and can go up 1000-fold as soon as stimulation is initiated, so it can immediately tell us how the disease is progressing. So CRP can be used to check the effectiveness of therapy or the progression of the disease. But besides its questionable use in everyday clinical practice as a cue for infection and/or inflammation, this protein has several other biological roles. Since CRP has opsonic activity and is capable of stimulating complement in the body, it is part of the host's natural protection against other microbes, including bacteria and fungi.
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Structure of Human C-reactive Protein
The overall length of the CRP pentamer is about 102 outer diameter, 30 at the center of the pore, and 36 at the protomer. Protome, 206 amino acids, folded into antiparallel jelly-roll sheets. The structure is very similar to SAP's, although each protein is different. A long helix is creased on one of the two sheets. The carboxyl end of the helix and loops 177–182 are one of two faces of a strange split that runs from the protomer's center to the pentamer's center pore. On the opposite end of the cleft are the amino and carboxyl termini of the protomer. The gulf is wide and deep at the source.
Biological Roles of C-Reactive Protein
CRP serves as a primary line of defense against pathogens. Despite its structural differences from immunoglobulin (Ig) molecules, CRP shares several functional properties with Igs, including the ability to promote agglutination, complement fixation, bacterial capsule swelling, phagocytosis, and the precipitation of polycationic and polyanionic compounds. Notable features of CRP include its binding specificity and site of synthesis, which classify it as a member of a new superfamily of proteins. Clinically, the quantitative estimation of CRP levels in serum is widely utilized as a sensitive marker of inflammation. Additionally, CRP plays a role in the clearance of bacteria, as well as dead and altered cells, and may also possess more complex immunomodulatory functions.
Fig. 1 C-reactive Protein has been studied as a screening tool for inflammation, a marker of disease activity, and a diagnostic aid (Rhodes, B.; et al. 2011).
Human C-reactive Protein and Metabolic Syndrome.
The most common biomarker of inflammation, CRP is an independent predictor of cardiovascular events in the future. There are multiple manifestations of metabolic syndrome (MetS): insulin resistance and obesity are its prominent hallmarks. API established five diagnostic features and any three [central obesity, dyslipidemia (high triglycerides, low HDL), hypertension, and impaired fasting glucose (IFG)] constitute a diagnosis of the syndrome. Increased CRP levels can increase cardiovascular risk in MetS patients, but more study is needed into the in vivo mechanisms of how CRP mediates vascular events and results in increased cardiovascular events in MetS patients.
- Human C-reactive protein-related diseases
- Nonspecific systemic necrotizing small vessel vasculitis
- Malignant myxoma of the left atrium
- Mucocutaneous lymph node syndrome
- Takayasu arteritis
- Microscopic polyangiitis
- Stimulitis-Johnson syndrome in children
- Takayasu arteritis in children
- Still's disease in adults
- Rheumatic fever
- Pneumonia in children
Characteristics of C-reactive Protein
Not only is CRP a nonspecific inflammatory marker, but it is also directly involved in cardiovascular diseases, including inflammation and atherosclerosis. Additionally, it serves as one of the strongest predictors and risk factors for cardiovascular disease. Through the collaboration between CRP and complement C1q and FcTR, it is possible for it to participate in many biological processes such as host defense against infection, phagocytosis inflammatory control, etc. By attaching to injured cells, apoptotic cells, and nuclear antigens, it is also relevant in autoimmune disorders.
Conclusion
CRP is an acute-phase protein mainly made by the liver and a biomarker of inflammation. It's a complex system, including the cell signaling systems, transcription factors, and inflammation factors that regulate CRP production. CRP is a product of the whole immune system and has changed with it. CRP's ligand-recognition activity can also lead to effector activity, so it is essential to have a thorough understanding of the biology of the CRP molecule.
References
- Pathak, A.; et al. Evolution of C-reactive protein. Frontiers in immunology. 2019, 10: 943.
- Ansar, W.; et al. C-reactive protein and the biology of disease. Immunologic research. 2013, 56: 131-142.
- Rhodes, B.; et al. C-reactive protein in rheumatology: biology and genetics. Nature Reviews Rheumatology. 2011, 7(5): 282-289.
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