L-ficolin Is a Pattern Recognition Molecule Specific for Acetyl Groups

Krarup, Anders; Thiel, Steffen; Hansen, Annette G.; Fujita, Teizo; Jensenius, Jens Christian

doi:10.1074/jbc.m407161200

Cited by 185 publications

(174 citation statements)

References 41 publications

(32 reference statements)

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“…Instead, recognition of these molecules appears to involve minimal structural requirement for the acetyl group, and virtually no requirement for the remainder of the molecule. Although this type of recognition was somewhat unexpected, it is fully consistent with the observed ability of a wide range of small acetylated compounds to partially inhibit the binding of L-ficolin to GlcNAc-Sepharose beads and to Streptococcus pneumoniae (Krarup et al, 2004).…”

Section: Structural Determinants For the Sensing Properties Of Human supporting

confidence: 78%

Deciphering complement mechanisms: The contributions of structural biology

Arlaud

Barlow

Gaboriaud

et al. 2007

Molecular Immunology

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Since the resolution of the first three-dimensional structure of a complement component in 1980, considerable efforts have been put into the investigation of this system through structural biology techniques, resulting in about a hundred structures deposited in the Protein Data Bank by the beginning of 2007. By revealing its mechanisms at the atomic level, these approaches significantly improve our understanding of complement, opening the way to the rational design of specific inhibitors. This review is co-authored by some of the researchers currently involved in the structural biology of complement and its purpose is to illustrate, through representative examples, how X-ray crystallography and NMR techniques help us decipher the many sophisticated mechanisms that underlie complement functions.

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Section: Structural Determinants For the Sensing Properties Of Human supporting

confidence: 78%

Deciphering complement mechanisms: The contributions of structural biology

Arlaud

Barlow

Gaboriaud

et al. 2007

Molecular Immunology

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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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“…H-ficolin (synonymous with ficolin-3 or Hakata-antigen) has a primary sequence that is 48% identical to that of L-ficolin and binds to GlcNAc, and D-fucose (14). The GlcNAc binding activity of H-ficolin, unlike that of L-ficolin, is not inhibited by acetyl compounds (31). M-ficolin (synonymous with ficolin-1 or Ficolin/ P35-related protein) has a primary sequence that is 80 and 48% identical to those of L-ficolin and H-ficolin, respectively (14,28).…”

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confidence: 99%

“…Lficolin (synonymous with ficolin-2 or Ficolin/P35) binds to GlcNAc (29,30) and GalNAc (8). The binding ability is inhibited by acetylated compounds, indicating that this protein specifically recognizes acetyl groups (31). L-ficolin activates the lectin complement pathway upon binding to lipoteichoic acid, a cell wall component of all Gram-positive bacteria (32).…”

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confidence: 99%

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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L-ficolin Is a Pattern Recognition Molecule Specific for Acetyl Groups

Cited by 185 publications

References 41 publications

Deciphering complement mechanisms: The contributions of structural biology

Deciphering complement mechanisms: The contributions of structural biology

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

Trivalent Recognition Unit of Innate Immunity System

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