Analysis of Binding Sites in Human C-reactive Protein for FcγRI, FcγRIIA, and C1q by Site-directed Mutagenesis

Bang, Ranhy; Marnell, Lorraine L.; Mold, Carolyn; Stein, Mary‐Pat; Clos, Kevin T. Du; Chivington-Buck, Corinn; Clos, Terry W. Du

doi:10.1074/jbc.m504782200

Cited by 86 publications

(89 citation statements)

References 49 publications

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“…His-38, Thr-173, and Leu-176 form part of the putative FcR binding site on CRP, and mutations of each one reduced both FcγR and C1q binding significantly (6,20). When these CRP mutants were assayed for FcαRI binding using BIAcore, H38A and L176A bound to the receptor similarly to wild-type CRP, but T173A showed increased FcαRI binding compared with the wild type (Fig.…”

Section: Resultsmentioning

confidence: 99%

Recognition and functional activation of the human IgA receptor (FcαRI) by C-reactive protein

Marjon

Marnell

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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C-reactive protein (CRP) is an important biomarker for inflammatory diseases. However, its role in inflammation beyond complement-mediated pathogen clearance remains poorly defined. We identified the major IgA receptor, FcαRI, as a ligand for pentraxins. CRP recognized FcαRI both in solution and on cells, and the pentraxin binding site on the receptor appears distinct from that recognized by IgA. Further competitive binding and mutational analysis showed that FcαRI bound to the effector face of CRP in a region overlapping with complement C1q and Fcγ receptor (FcγR) binding sites. CRP cross-linking of FcαRI resulted in extracellular signal-regulated kinase (ERK) phosphorylation, cytokine production, and degranulation in FcαRI-transfected RBL cells. In neutrophils, CRP induced FcαRI surface expression, phagocytosis, and TNF-α secretion. The ability of CRP to activate FcαRI defines a function for pentraxins in inflammatory responses involving neutrophils and macrophages. It also highlights the innate aspect of otherwise humoral immunity-associated antibody receptors.

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Section: Resultsmentioning

confidence: 99%

Recognition and functional activation of the human IgA receptor (FcαRI) by C-reactive protein

Marjon

Marnell

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…More specifically, CRP binds to the surface of apoptotic cells, invading microbes or 'altered' cells and activates the classic complement pathway, enhancing opsonization and phagocytosis of CRP-tagged targets [21,22]. On the other hand, CRP recruits C4b-binding protein (the major inhibitor of the classic pathway) and modulates the activity of immune cells (neutrophils, monocytes and macrophages) [19].…”

Section: Discussionmentioning

confidence: 99%

Baseline and postoperative C-reactive protein levels predict mortality in operable lung cancer

Pastorino

Morelli

Leuzzi

et al. 2017

European Journal of Cancer

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Background: Higher blood levels of C-reactive protein (CRP) have been associated with shorter survival in patients with cardiovascular, chronic obstructive pulmonary disease and cancer. We investigated the impact of baseline and postoperative CRP levels on survival of patients with operable lung cancer (LC). Patients and methods: CRP values at baseline (CRP 0 ) and 3 days after surgery (CRP 3 ) were measured in a consecutive series of 1750 LC patients who underwent complete resection between 2003 and 2015. Patients were classified as having 0 (N Z 593), 1 (N Z 658) or 2 (N Z 553) risk factors: CRP 0 and/or CRP 3 values above the respective median value. The effect of higher CRP was evaluated by KaplaneMeier mortality curves and adjusted hazard ratio (HR) with 95% confidence interval (CI), by fitting Cox proportional hazards models. Results: Cumulative proportions of 5-year survival were 67% for 0 risk factors, 58% for 1 risk factor and 41% for 2 risk factors (P < 0.0001). The overall 5-year mortality risk was significantly higher in patients with 1 risk factor (adjusted hazard ratio [aHR] 1.43 [95% CI 1.14e1.79]), or 2 risk factors (aHR 2.49 [95% CI 1.99e3.11]). A significant impact on survival was observed in each tumour-node-metastasis stage group, and in the subset of non-smokers. Postoperative 30-

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“…On the hCRP effector face, C1q and FcR share an identical a-helical region for binding, the centre pore boundary (Bang et al, 2005;Gaboriaud et al, 2003;Lu et al, 2008). However, the Dare-PTX pore differs from that of hCRP (Fig.…”

Section: A New C1q Binding Mode In Dare-ptxmentioning

confidence: 99%

Crystal structures for short-chain pentraxin from zebrafish demonstrate a cyclic trimer with new recognition and effector faces

Chen

Yuan

et al. 2015

Journal of Structural Biology

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Analysis of Binding Sites in Human C-reactive Protein for FcγRI, FcγRIIA, and C1q by Site-directed Mutagenesis

Cited by 86 publications

References 49 publications

Recognition and functional activation of the human IgA receptor (FcαRI) by C-reactive protein

Recognition and functional activation of the human IgA receptor (FcαRI) by C-reactive protein

Baseline and postoperative C-reactive protein levels predict mortality in operable lung cancer

Crystal structures for short-chain pentraxin from zebrafish demonstrate a cyclic trimer with new recognition and effector faces

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