Characterization of FIBCD1 as an Acetyl Group-Binding Receptor That Binds Chitin

Abstract

Chitin is a highly acetylated compound and the second most abundant biopolymer in the world next to cellulose. Vertebrates are exposed to chitin both through food ingestion and when infected with parasites, and fungi and chitin modulate the immune response in different directions. We have identified a novel homotetrameric 55-kDa type II transmembrane protein encoded by the FIBCD1 gene and highly expressed in the gastrointestinal tract. The ectodomain of FIBCD1 is characterized by a coiled-coil region, a polycationic region and C-terminal fibrinogen-related domain that by disulfide linkage assembles the protein into tetramers. Functional analysis showed a high-affinity and calcium-dependent binding of acetylated components to the fibrinogen domain, and a function in endocytosis was demonstrated. Screening for ligands revealed that the FIBCD1 is a high-affinity receptor for chitin and chitin fragments. FIBCD1 may play an important role in controlling the exposure of intestine to chitin and chitin fragments, which is of great relevance for the immune defense against parasites and fungi and for immune response modulation.

The Recognition Unit of FIBCD1 Organizes into a Noncovalently Linked Tetrameric Structure and Uses a Hydrophobic Funnel (S1) for Acetyl Group Recognition

“…FIBCD1 is expressed apically on enterocytes in the small and large intestine, and functional analyses in human cells have shown that FIBCD1 mediates endocytosis of its ligands. Furthermore, the FIBCD1-FReD binds selectively and calciumdependently to acetylated structures including chitin, some N-acetylated carbohydrates and amino acids, but not to their nonacetylated counterparts, confirming that the acetyl group binding properties of FIBCD1 lies within the FReD (1). Chitin, the most abundant biopolymer next to cellulose, is a linear homopolymer of ␤-1,4-linked N-acetyl glucosamines (GlcNAc), which is commonly found in organisms such as fungi, insects, and crustaceans but not in mammals.…”

“…The rabbit was bled 10 days after the last injection, and the serum was kept at 4°C. Davids Biotechnology, (Regensburg, Germany) performed the immunizations of the chicken and the purification of anti-FIBCD1 antibodies as described (1).…”

“…We have previously shown that FIBCD1-ECPs bind acetylated structures (1). To test whether the FIBCD1-FReDs are sufficient for ligand interactions, we compared the binding of FIBCD1-ECPs and FIBCD1-FReDs to acetylated BSA in competition assays with various acetylated and nonacetylated carbohydrates, and the concentrations of the substances that resulted in a 50% inhibition (IC 50 ) of acetylated BSA binding were calculated.…”

“…We have recently identified FIBCD1 as the first vertebrate membrane-bound chitin-binding protein (1). FIBCD1 is a type II transmembrane receptor composed of a cytoplasmic tail with two potential phosphorylation sites, a transmembrane helix, and an ectodomain.…”

Recognition and Blocking of Innate Immunity Cells by Candida albicans Chitin

“…Recent work has revealed several chitin-binding proteins, such as RegIIIg (HIP/ PAP), a C-type lectin expressed in the neutrophil-like Paneth cells of the small intestine (6), and FIBCD1, a calcium-dependent acetyl group-binding receptor that is also expressed in the gastrointestinal tract (47), although no chitin receptor in myeloid cells of the immune system has thus far been identified.…”