Qually to this work. two To whom correspondence need to be addressed. Tel.: 0-1782-733419; Fax: 0-1782-733516; E-mail: [email protected] recognition domain containing 1 (FIBCD1)3 is a recently found vertebrate acetyl group recognition receptor that binds chitin (1). FIBCD1 forms tetramers in the plasma membrane, and every in the chains from the homotetrameric protein consists of a short cytoplasmic tail, a trans-membrane helix, and an ectodomain containing a coiled-coil region, a polycationic area, and also a C-terminal fibrinogen-like recognition domain (FReD). FIBCD1 is expressed primarily apically on enterocytes and on airway epithelial cells, but in addition on epithelial cells lining the salivary ducts. FIBCD1 mediates endocytosis of its bound ligand which can be released towards the surroundings right after degradation, with FIBCD1 being recycled towards the plasma membrane. Two prospective phosphorylation web pages within the cytoplasmic portion of FIBCD1 suggest that FIBCD1 also may perhaps be a signaling protein. The FIBCD1 gene is localized on chromosome 9q34.1 in close proximity for the genes encoding L- and M-ficolin (2). The FReD of FIBCD1 shows high homology to the vertebrate innate immune proteins L-ficolin and M-ficolin and towards the horseshoe crab protein tachylectin 5A (TL5A) that all bind acetyl groups by way of the fibrinogen-related domain (Fig. 1). FIBCD1 especially binds acetylated elements such as chitin, but fails to bind lipopolysaccharides (LPS), lipoteichoic acid, mannan, or peptidoglycan (1), the last consisting of GlcNAc and MurNAc residues arranged in a structure equivalent to that on the (GlcNAc)n structure of chitin. This binding is in contrast to L-ficolin whose known ligands, along with acetyl groups (3), consist of lipoteichoic acid and -1,3-glucan (four), and to TL5A, which recognizes the O-antigen of LPS (five). An extended binding surface that incorporates four binding web pages designated S1 four, has beenThe abbreviations applied are: FIBCD1, fibrinogen C domain containing 1; FReD, fibrinogen-like recognition domain; TL5A, tachylectin 5A.2880 JOURNAL OF BIOLOGICAL CHEMISTRYVOLUME 289 ?Number five ?JANUARY 31,Crystal Structure of FIBCDFIGURE 1. Alignment and sequence homology (identity) from the fibrinogen-like domains of FIBCD1, TL5A, L-ficolin, M-ficolin, and H-ficolin according to structural superposition. Sequence numbers and secondary structure elements around the best refer towards the FIBCD1 sequence together with the numbering in the helices and strands according to the secondary structure components assigned in TL5A and L-ficolin. The loops L1, L2, and L3 (see “Results”) are indicated. The S1 and calcium binding web site residues are highlighted in green (S1) and yellow respectively, with all the S3 binding website highlighted in gray.Buy2-Chloro-6-fluoro-1H-benzo[d]imidazole Residues that bind the added sulfate in proximity to S1 are boxed.Buy3-(2,5-Dichloropyrimidin-4-yl)-1H-indole identified in L-ficolin, with many carbohydrate and noncarbohydrate ligands binding to internet sites S2 4 (6).PMID:24423657 In contrast to TL5A (7) and M-ficolin (eight), which particularly bind N-acetyl groups in web-site S1, acetylated ligands bind to L-ficolin in either S2 or S3 based on the nature of your ligand (six). The higher homology to the ficolins, that are well characterized pattern recognition molecules that play critical roles in innate immunity, and also the place at the apical part of mucosal epithelial cells suggest that FIBCD1 plays a vital part in innate immunity. The oligomeric state of FIBCD1 supports this, as oligomerization permits structural arrangement to ensure that an proper numbe.