Ficolins/Mannose-binding protein

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The ficolins share a common organization and function with the collectins: serum mannose-binding and the pulmonary surfactant proteins A and D. All of these proteins are soluble mediators of innate immunity and consist of globular sugar-binding domains attached to collagenous stalks, which can invoke innate immune responses either through complement fixation or interaction with receptors on the surfaces of macrophages. Amongst these proteins, the ficolins have been most extensively investigated with CFG resources, while mannose-binding protein is the best characterized. The ficolins have fibrinogen-like sugar-binding domains, rather than C-type carbohydrate-recognition domains, but conceptually fall within the same group.

See also: paradigm page for Ficolin M (Ficolin 1)


CFG Participating Investigators contributing to the understanding of this paradigm

Participating Investigators have generated and characterized knockout mice, defined the sugar-binding properties and undertaken structural analysis for members of this glycan-binding protein (GBP) group.

  • PIs working on ficolins include: Raymond Dwek, Daniel Mitchell, Nicole Thielens
  • PIs investigating other paradigms in this GBP group include: Kurt Drickamer, Ten Feizi, Toshisuke Kawasaki, Laura Kiessling, Reiko Lee, Yuan Lee, Jamie Marth, Kenneth Ng, Michel Nussenzweig, Pauline Rudd, Maureen Taylor, Bill Weis
  • Non-PIs with who have used CFG resources to study ficolins include: David Stephens

Progress toward understanding this GBP paradigm

This section documents what is currently known about mannose-binding protein, its carbohydrate ligand(s), and how they interact to mediate cell communication. Further information can be found in the GBP Molecule Pages for human and mouse mannose-binding protein in the CFG database.

Carbohydrate ligands

L-ficolin preferentially recognizes disulfated LacNAc and tri- and tetrasaccharides containing a terminal LacNAc or GlcNAc unit, provided that the linkage with the following carbohydrate is not of the β1-3 type[1][2]. H-ficolin does not bind to any of the glycans.

Mannose-binding protein, also known as mannan-binding lectin (MBL), binds to terminal mannose, fucose and GlcNAc residues on the outer surfaces of bacterial and fungal cell walls. MBL belongs to a family of soluble immune proteins known as the collectins that consist of N-terminal collagen tail regions and C-terminal C-type lectin domains. Other family members include lung surfactant protein A (SP-A) that preferentially binds to galactose, mannose and fucose residues on microbial glycolipids [3], and lung surfactant protein D (SP-D) that has been shown to interact with mannoside and glucoside moieties. [4]

Cellular expression of GBP and ligands

Mannose-binding protein is produced mostly by hepatocytes and secreted into the circulation. SP-A and SP-D are produced mostly by alveolar cells and secreted to the pulmonary surfactant that lines the lung.
L- and H-ficolins are serum proteins that are essentially synthesized in the liver. H-ficolin is also synthesized by bile duct epithelial cells, by lung ciliated bronchial and type II alveolar epithelial cells, and by glioma cells [5][6].

Biosynthesis of ligands


The 3-D structures of the trimeric fibrinogen-like recognition domains of L- and H-ficolins have been solved by X-ray crystallography, revealing similar three-lobed clover-like assemblies, whereas different recognition mechanisms have been deciphered from the structure of complexes with various ligands[7]. An external ligand binding site able to accommodate neutral carbohydrates such as galactose and D-fucose has been identified for H-ficolin. In contrast, L-ficolin exhibited three additional binding sites which define a continuous recognition surface able to bind acetylated and neutral carbohydrates in the context of extended polysaccharides such as 1,3-β-D-glucan.

Biological roles of GBP-ligand interaction

Ficolins share with mannan-binding lectin the ability to associate with mannan-binding lectin- associated serine protease-2, thus triggering activation of the lectin complement pathway upon binding to suitable targets and enhancing their phagocytosis. L-ficolin recognizes several strains of opportunistic capsulated bacteria and Salmonella typhimurium whereas H-ficolin specifically recognizes Aerococcus viridans. In addition to pathogenic microorganisms, L- ficolin binds specifically to apoptotic HL60, U937 and Jurkat T cells, whereas binding of H-ficolin is restricted to apoptotic Jurkat T cells [8][9][10].

CFG resources used in investigations

The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for ficolin and mannose-binding receptor.

Glycan profiling

Glycogene microarray

Knockout mouse lines

Glycan array

The binding specificities of several of the ficolins have been analyzed and other members of the group were screened on the CFG glycan array.
Investigators have used CFG glycan arrays to study ligand binding specificity of human L-ficolin (see examples here, here, here, here, and here) and of its rat homologue ficolin A (see example here). Several analyses with human H-ficolin, which has no homologue in rodents, yielded inconclusive results (see examples here, here, here, here, and here). See all glycan array results for ficolin here.

Related GBPs

Serum mannose-binding protein (MBP, also designated mannose-binding lectin, MBL) and the pulmonary surfactant proteins SP-C and SP-D


  1. Gout E, Garlatti V, Smith DF, Lacroix M M, Dumestre-Perard C, Lunardi T, Martin L, Cesbron JY, Arlaud GJ, Gaboriaud C, Thielens NM (2010) Carbohydrate recognition properties of human ficolins: Glycan array screening reveals the sialic acid binding specificity of M-ficolin. J Biol Chem 285:6612-22
  2. Krarup A, Mitchell DA, Sim RB (2008) Recognition of acetylated oligosaccharides by human L-ficolin. Immunol Lett 118:152-6
  3. Childs RA, Wright JR, Ross GF, Yuen CT, Lawson AM, Chai W, Drickamer K, Feizi T (1992) Specificity of lung surfactant protein SP-A for both the carbohydrate and the lipid moieties of certain neutral glycolipids. J Biol Chem 267:9972-9
  4. Shrive AK, Martin C, Burns I, Paterson JM, Martin JD, Townsend JP, Waters P, Clark HW, Kishore U, Reid KB, Greenhough TJ (2009) Structural characterisation of ligand-binding determinants in human lung surfactant protein D: influence of Asp325. J Mol Biol 394:776-88.
  5. Akaiwa M, Yae Y, Sugimoto R, Suzuki SO, Iwaki T, Izuhara K, Hamasaki N (1999) Hakata antigen, a new member of the ficolin/opsonin p35 family, is a novel human lectin secreted into bronchus/alveolus and bile. Histochem Cytochem 47:777-86
  6. Kuraya M, Matsushita M, Endo Y, Thiel S, Fujita T (2003) Expression of H-ficolin/Hakata antigen, mannose-binding lectin-associated serine protease (MASP)-1 and MASP-3 by human glioma cell line T98G. Int Immunol 2003:15:109-17
  7. Garlatti V, Belloy N, Martin L, Lacroix M, Matsushita M, Endo Y, Fujita T, Fontecilla-Camps JC, Arlaud GJ, Thielens NM, Gaboriaud C (2007) Structural insights into the innate immune recognition specificities of L- and H-ficolins. EMBO J 26:623-33
  8. Kuraya M, Ming Z, Liu X, Matsushita M, Fujita T (2005) Specific binding of L-ficolin and H-ficolin to apoptotic cells leads to complement activation. Immunobiology 209:689-97
  9. Honoré C, Hummelshoj T, Hansen BE, Madsen HO, Eggleton P, Garred P(2007) The innate immune component ficolin 3 (Hakata antigen) mediates the clearance of late apoptotic cells. Arthritis Rheum 56:1598-1607
  10. Jensen ML, Honoré C, Hummelshøj T, Hansen BE, Madsen HO, Garred P(2007) Ficolin-2 recognizes DNA and participates in the clearance of dying host cells. Mol Immunol 44:856-65


The CFG is grateful to the following PIs for their contributions to this wiki page: Kurt Drickamer, Nicole Thielens, Daniel Mitchell, Yvette van Kooyk

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