Calcium ion binding regions in C-reactive protein: Location and regulation of conformational changes

Mullenix, Michael C.; Mortensen, Richard F.

doi:10.1016/0161-5890(94)90169-4

Cited by 13 publications

(18 citation statements)

References 25 publications

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“…Previous studies have described how two Ca 2+ binding sites in the CRP pentamer [18] directly bind to two oxygen atoms within a phosphate group of PC [19], while specific binding sites for FcγRs are located on the opposite plane of CRP [20]. Electron microscopy studies have demonstrated that binding of CPR to PC-containing ligands, including LPC, induces the partial dissociation of the pentameric structure of CRP to an open-ring-like structure [21].…”

Section: Discussionmentioning

confidence: 99%

The pro-atherogenic effects of macrophages are reduced upon formation of a complex between C-reactive protein and lysophosphatidylcholine

et al. 2012

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RationaleC-reactive protein (CRP) and lysophosphatidylcholine (LPC) are phosphorylcholine-(PC)-containing oxidized phospholipids (oxPLs) found in oxidized LDL (oxLDL), which trigger pro-atherogenic activities of macrophages during the process of atherosclerosis. It has been previously reported that CRP binds to the PC head group of oxLDL in a calcium-dependent manner. The aim of this study was to investigate the importance of binding between CRP and LPC to the pro-atherogenic activities of macrophages.Objectives and findingsA chemiluminescent immunoassay and HPLC showed that human recombinant CRP formed a stable complex with LPC in the presence of calcium. The Kd value of the binding of the CRP-LPC complex to the receptors FcγRIA or FcγRIIA was 3–5 fold lower than that of CRP alone. The CRP-LPC complex triggered less potent generation of reactive oxygen species and less activation of the transcription factors AP-1 and NF-kB by human monocyte-derived macrophages in comparison to CRP or LPC alone. However, CRP did not affect activities driven by components of oxLDL lacking PC, such as upregulation of PPRE, ABCA1, CD36 and PPARγ and the enhancement of cholesterol efflux by human macrophages. The presence of CRP inhibited the association of Dil-labelled oxLDL to human macrophages.ConclusionsThe formation of complexes between CRP and PC-containing oxPLs, such as LPC, suppresses the pro-atherogenic effects of CRP and LPC on macrophages. This effect may in part retard the progression of atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

The pro-atherogenic effects of macrophages are reduced upon formation of a complex between C-reactive protein and lysophosphatidylcholine

et al. 2012

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“…1). Each CRP subunit binds two calcium ions (2). At physiological pH, CRP binds to molecules and cells bearing exposed phosphocholine (PCh) moieties, such as pneumococcal C-polysaccharide (PnC), in a Ca 2ϩ -dependent manner (3,4).…”

Section: C-reactive Protein (Crp)mentioning

confidence: 99%

Exposing a Hidden Functional Site of C-reactive Protein by Site-directed Mutagenesis

Singh

Thirumalai

Hammond

et al. 2012

Journal of Biological Chemistry

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Background:The functions of C-reactive protein (CRP) in the extracellular matrix at the sites of inflammation are unknown. Results: Mutation of just one amino acid in CRP (E42Q) expands its ligand-binding capacity. Conclusion: Some functions of CRP depend upon its inflammation-induced structural configuration. Significance: Investigations using E42Q-CRP in animal models of inflammatory diseases may establish its therapeutic potential, the functions of CRP, and a CRP-targeting strategy.

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“…1,2 CRP has an important host/ defence function, which may be through its capacity for calcium-dependent binding to molecules containing phosphorylcholine. 3 It has been reported that in immunoturbidimetric assays, lower values of CRP are found in serum than in EDTA plasma, especially where the CRP concentration is 520 mg/L. 4 Serum is the preferred specimen for CRP measurement.…”

Section: Introductionmentioning

confidence: 99%

Interference caused by the contents of serum separator tubes in the Vitros CRP assay

et al. 2003

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Calcium ion binding regions in C-reactive protein: Location and regulation of conformational changes

Cited by 13 publications

References 25 publications

The pro-atherogenic effects of macrophages are reduced upon formation of a complex between C-reactive protein and lysophosphatidylcholine

The pro-atherogenic effects of macrophages are reduced upon formation of a complex between C-reactive protein and lysophosphatidylcholine

Exposing a Hidden Functional Site of C-reactive Protein by Site-directed Mutagenesis

Interference caused by the contents of serum separator tubes in the Vitros CRP assay

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