Effect of Capsulation of Opportunistic Pathogenic Bacteria on Binding of the Pattern Recognition Molecules Mannan-Binding Lectin, L-Ficolin, and H-Ficolin

Krarup, Anders; Sørensen, Uffe B. Skov; Matsushita, Misao; Jensenius, Jens C.; Thiel, Steffen

doi:10.1128/iai.73.2.1052-1060.2005

Cited by 176 publications

(183 citation statements)

References 44 publications

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“…This also means that the surfaces of some pathogens can induce the formation of the active conformation of the FBG domains and thereby increase the avidity for the surface. Indeed, the binding specificity for various bacteria differs among ficolins (9,20,22,29,32,45). Such surface-dependent conformational changes would facilitate the discrimination between self and non-self.…”

Section: Discussionmentioning

confidence: 99%

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Trivalent Recognition Unit of Innate Immunity System

Tanio

Kondo

Sugio

et al. 2007

Journal of Biological Chemistry

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Ficolins are a kind of pathogen-recognition molecule in the innate immune systems. To investigate the discrimination mechanism between self and non-self by ficolins, we determined the crystal structure of the human M-ficolin fibrinogen-like domain (FD1), which is the ligand-binding domain, at 1.9 Å resolution. Although the FD1 monomer shares a common fold with the fibrinogen ␥ fragment and tachylectin-5A, the Asp-282-Cys-283 peptide bond, which is the predicted ligand-binding site on the C-terminal P domain, is a normal trans bond, unlike the cases of the other two proteins. The trimeric formation of FD1 results in the separation of the three P domains, and the spatial arrangement of the three predicted ligand-binding sites on the trimer is very similar to that of the trimeric collectin, indicating that such an arrangement is generally required for pathogen-recognition. The ligand binding study of FD1 in solution indicated that the recombinant protein binds to N-acetyl-D-glucosamine and the peptide Gly-Pro-Arg-Pro and suggested that the ligand-binding region exhibits a conformational equilibrium involving cis-trans isomerization of the Asp-282-Cys-283 peptide bond. The crystal structure and the ligand binding study of FD1 provide an insight of the self-and non-self discrimination mechanism by ficolins.Surveillance systems of innate immunity are present in all multicellular organisms and play a crucial role in the first line of defense against pathogens. Ficolins, as well as collectins, are one of the most important groups of pattern recognition molecules in the innate immunity systems (1-7) and have been identified in both vertebrates and invertebrates (6). Ficolins are comprised of a collagen-like domain at the N terminus and a fibrinogen-like domain (FBG), 3 which is the sugar-binding site, at the C terminus (8, 9). Collectins, such as mannose-binding lectin (MBL), lung surfactant protein A, and surfactant protein D, also consist of an N-terminal collagen-like domain and a C-terminal carbohydrate-recognition domain (CRD) that binds to certain carbohydrates such as mannose and GlcNAc Ca 2ϩ dependently. The CRD on MBL, surfactant protein A, and surfactant protein D forms a trimeric structure through a triple ␣-helical coiled-coil at a short neck region between the collagen-like domain and the CRD (10 -12). Ficolins also form trimers (8,13,14), although the mechanism of trimerization is unclear. Both ficolins and collectins form trimer-based multimers that are N-terminally linked by disulfide bonds (15). Ficolins and MBL also interact with MBL-associated serine proteases, and their complexes activate the lectin complement pathway (6, 16 -23).Ficolins were originally discovered in porcine uterus membrane extracts as transforming growth factor-␤-binding proteins (24,25). In human, L-ficolin and H-ficolin in serum and M-ficolin in cells have been characterized (9, 14, 26 -29). Lficolin (synonymous with ficolin-2 or Ficolin/P35) binds to GlcNAc (29, 30) and GalNAc (8). The binding ability is inhibited by acetylated c...

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Section: Discussionmentioning

confidence: 99%

“…Since the corresponding residues of the ligandbinding site in H-ficolin differ from those in L-ficolin, Mficolin, and TL5A, its manner of ligand binding may differ. These differences would contribute to the range of pathogen recognition specificity (9,20,22,29,32,45).…”

Section: Discussionmentioning

confidence: 99%

Trivalent Recognition Unit of Innate Immunity System

Tanio

Kondo

Sugio

et al. 2007

Journal of Biological Chemistry

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“…The lectin pathway via MBL has both antibody-dependent and antibody-independent modes of activation. H and L ficolins have been shown to bind to a range of bacterial species (Krarup et al, 2005). M-ficolin is a cell-surface protein that has not been widely studied yet.…”

Section: Introductionmentioning

confidence: 99%

Complement genetics, deficiencies, and disease associations

Mayilyan

2012

Protein Cell

149

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The complement system is a key component of innate immunity. More than 45 genes encoding the proteins of complement components or their isotypes and subunits, receptors, and regulators have been discovered. These genes are distributed throughout different chromosomes, with 19 genes comprising three significant complement gene clusters in the human genome. Genetic deficiency of any early component of the classical pathway (C1q, C1r/s, C2, C4, and C3) is associated with autoimmune diseases due to the failure of clearance of immune complexes (IC) and apoptotic materials, and the impairment of normal humoral response. Deficiencies of mannan-binding lectin (MBL) and the early components of the alternative (factor D, properdin) and terminal pathways (from C3 onward components: C5, C6, C7, C8, C9) increase susceptibility to infections and their recurrence. While the association of MBL deficiency with a number of autoimmune and infectious disorders has been well established, the effects of the deficiency of other lectin pathway components (ficolins, MASPs) have been less extensively investigated due to our incomplete knowledge of the genetic background of such deficiencies and the functional activity of those components. For complement regulators and receptors, the consequences of their genetic deficiency vary depending on their specific involvement in the regulatory or signalling steps within the complement cascade and beyond. This article reviews current knowledge and concepts about the genetic load of complement component deficiencies and their association with diseases. An integrative presentation of genetic data with the latest updates provides a background to further investigations of the disease association investigations of the complement system from the perspective of systems biology and systems genetics.

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“…L-ficolin binds to GlcNAc residue next to galactose at the nonreducing terminal of the oligosaccharide (21). Several reports recently showed that L-ficolin could bind to various acetylated compounds, 1,3-β-D glucan, a molecular marker of yeast and fungal cell walls, lipopolysaccharide (LPS) on gram-negative bacterial species and Lipoteichoic Acid (LTA) on the gram-positive bacteria Staphylococcus aureus and Streplococcus pneumoniae, following the activation of complement (22)(23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

Specifically Binding of L-ficolin to N-glycans of HCV Envelope Glycoproteins E1 and E2 Leads to Complement Activation

Liu

Ali

et al. 2009

Cell Mol Immunol

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L-ficolin, one of lectin families, is a recently identified complement factor that initiates lectin pathway of complement. Little is known about its role in viral hepatitis. In the present study, we found that L-ficolin in serum from 103 patients with hepatitis C virus (HCV), were significantly higher than that in 150 healthy controls. We further found that L-ficolin expressions were significantly increased in vitro study by HCV JFH-1 infected human hepatocyte cell line Huh7.5.

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Effect of Capsulation of Opportunistic Pathogenic Bacteria on Binding of the Pattern Recognition Molecules Mannan-Binding Lectin, L-Ficolin, and H-Ficolin

Cited by 176 publications

References 44 publications

Trivalent Recognition Unit of Innate Immunity System

Trivalent Recognition Unit of Innate Immunity System

Complement genetics, deficiencies, and disease associations

Specifically Binding of L-ficolin to N-glycans of HCV Envelope Glycoproteins E1 and E2 Leads to Complement Activation

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