Antigenic, electrophoretic and binding alterations of human C-reactive protein modified selectively in the absence of calcium

Potempa, Lawrence A.; Maldonado, B. A.; Laurent, Philippe; Zemel, E. S.; Gewürz, Henry

doi:10.1016/0161-5890(83)90140-2

Cited by 138 publications

(113 citation statements)

References 27 publications

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“…6 The structural changes releasing CRP subunits from the pentamer are correlated with expression of a new antigenic reactivity and formation of neo-epitopes. 7 The forms of CRP expressing …”

Section: Studies On the Interactions Between C-reactive Protein And Cmentioning

confidence: 99%

Studies on the interactions between C‐reactive protein and complement proteins

et al. 2007

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Studies on the interactions between C-reactive protein and complement proteins IntroductionThe classical acute-phase reactant C-reactive protein (CRP) is a pentameric, disc-shaped serum protein.1 Its basic features are the control of inflammation, the stimulation of clearance of damaged cell and tissue components, and the initiation of repair functions.2 CRP shows calcium-dependent affinity for phosphate monoesters, such as phosphatidylcholine, but several other ligands of CRP have been characterized, including damaged cell membranes, small ribonucleoprotein particles, apoptotic cells and fibronectin. Native CRP can undergo subunit dissociation into individual monomeric units, for example upon association with negatively charged lipid monolayers. 4 This modified form of CRP can be produced in vitro by urea chelation, acid treatment, heating or direct immobilization of native CRP onto polystyrene.5 This modified form of CRP (mCRP) has reduced solubility and exhibits different electrophoretic characteristics as the result of a decrease of isoelectric point (pI) from 6Á4 to 5Á4. 6 The structural changes releasing CRP subunits from the pentamer are correlated with expression of a new antigenic reactivity and formation of neo-epitopes. 7 The forms of CRP expressing SummarySeveral studies have investigated the interactions between C-reactive protein (CRP) and various complement proteins but none of them took into consideration the different structural forms of CRP. The aim of our study was to investigate whether the different antigenic forms of CRP are able to bind C1q, to trigger activation of the C1 complex and to study the ability of the various CRP forms to bind complement factor H (FH) and C4b-binding protein (C4BP). Interactions between various CRP forms and complement proteins were analysed in enzyme-linked immunosorbent assay and surface plasmon resonance tests and activation of the C1 complex was followed in a reconstituted system using purified C1q, C1r and C1s in the presence of C1-INH. Native, ligand-unbound CRP activated the classical pathway weakly. After binding to phosphocholine, native CRP bound C1q and significantly activated C1. Native CRP complexed to phosphocholine did not bind the complement regulatory proteins FH and C4BP. After disruption of the pentameric structure of CRP, as achieved by urea-treatment or by site-directed mutagenesis, C1q binding and C1 activation further increased and the ability of CRP to bind complement regulatory proteins was revealed. C1q binds to CRP through its globular head domain. The binding sites on CRP for FH and C4BP seemed to be different from that of C1q. In conclusion, in parallel with the increase in the C1-activating ability of different CRP structural variants, the affinity for complement regulatory proteins also increased, providing the biological basis for limitation of excess complement activation.

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Section: Studies On the Interactions Between C-reactive Protein And Cmentioning

confidence: 99%

Studies on the interactions between C‐reactive protein and complement proteins

et al. 2007

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“…45 The modified CRP runs faster in gel electrophoresis and has lower solubility than native CRP. 40 pCRP is formed by urea-chelation treatment and resembles the free subunit mCRP.…”

Section: Figure 5: Degradation Products Of Crp and Their Functionsmentioning

confidence: 99%

C - reactive protein: An inflammatory marker with specific role in physiology, pathology, and diagnosis

Chandrashekara¹

2014

IJRCI

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“…"mCRP" is also used as the abbreviation for "modified CRP" because the conversion to mCRP is usually accompanied by significant alterations in the native subunit structure and epitope expression. Accordingly, a significant loss of secondary structural elements and a marked relaxation of the tertiary packing have been demonstrated upon dissociation of CRP to mCRP [54][55][56]. Presumably due to the prominent conformation rearrangement, mCRP is unable to spontaneously re-associate back to the cyclic pentameric CRP [57]; rather, this molecule is prone to aggregating into high-order oligomers composed of tens of monomers [58].…”

Section: The Bioactivities Of Crp Are Dependent On Conformational Statesmentioning

confidence: 99%

“…This hypothesis thus implicates the dissociation of CRP as a key mechanism that acts as a firewall to avoid fluctuations in the serum levels of CRP to generate immediate global effects. However, the concept of mCRP has been disputed for decades since its first demonstration by Potempa et al [54] in the early 1980s. The major concern is that the structure of the CRP molecule is exceptionally stable in the presence of calcium [1] and the preparation of mCRP requires highly denaturing treatments of CRP with concomitant chelation of calcium [54].…”

Section: Dissociation Of Crp Localizes the Enhanced Bioactivitiesmentioning

confidence: 99%

“…However, the concept of mCRP has been disputed for decades since its first demonstration by Potempa et al [54] in the early 1980s. The major concern is that the structure of the CRP molecule is exceptionally stable in the presence of calcium [1] and the preparation of mCRP requires highly denaturing treatments of CRP with concomitant chelation of calcium [54]. Therefore, the identification of dissociation pathways with a pathophysiological relevance is of paramount importance.…”

Section: Dissociation Of Crp Localizes the Enhanced Bioactivitiesmentioning

confidence: 99%

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Regulated conformation changes in C-reactive protein orchestrate its role in atherogenesis

2012

Chin. Sci. Bull.

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C-reactive protein (CRP) is a prototypic human acute phase reactant composed of five identical subunits. Emerging evidence indicates that CRP is not merely a predictor of cardiovascular disease, but may also be a direct mediator. However, the diverse and sometimes contradictory activities of CRP have considerably hampered the attempts to define the exact role of CRP in atherogenesis. Here, we review the multiple layers of regulation of CRP's structure and function, highlighting how local inflammation conditions, such as the abundance of damaged cell membranes and redox homeostasis, can tip the balance of the pro-and antiinflammatory activities of CRP. We propose that the highly controlled interplay between different structural conformations of CRP underlies its intrinsic property as a fine modulator of inflammation and atherogenesis. C-reactive protein, inflammation, atherosclerosis, redox Citation:Ma X, Ji S R, Wu Y. Regulated conformation changes in C-reactive protein orchestrate its role in atherogenesis.

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Antigenic, electrophoretic and binding alterations of human C-reactive protein modified selectively in the absence of calcium

Cited by 138 publications

References 27 publications

Studies on the interactions between C‐reactive protein and complement proteins

Studies on the interactions between C‐reactive protein and complement proteins

C - reactive protein: An inflammatory marker with specific role in physiology, pathology, and diagnosis

Regulated conformation changes in C-reactive protein orchestrate its role in atherogenesis

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