Ficolins

The human ficolins are homooligomers. Each subunit is composed of an N-terminal region including two cysteine residues, a collagen-like domain, a neck region and a fibrinogen-like domain. Electron microscopy of the whole proteins of human ficolin-2 and ficolin-3 show bouquet-like images, similar to those first described for C1q. All human ficolins recognise N-acetylated carbohydrates and compounds such as N-acetylglucosamine (GlcNAc) in common, although the spectrum of ligands for each ficolin is slightly different. Human ficolin-1 binds sialic acid, and human ficolin-3 recognises d-fucose and galactose. Ficolin-2 exhibits broad binding specificities due to it having four distinct binding sites in the fibrinogen-like domain that allow it to bind various carbohydrates, including β-(1,3)-d-glucan and peptideglycan, and sulphated carbohydrates, including heparin, while ficolin-1 and ficolin-3 have only one binding site. In addition to carbohydrates, ficolin-1 binds to tectonin9, and ficolin-2 binds elastin, corticosteroid11 and DNA. Each ficolin is able to bind to a spectrum of bacteria. Ficolin-1 and ficolin-2 interact with C-reactive protein, boosting both the lectin and classical pathway. A low concentration of ficolin-1 is also present in the serum with the mean level of 1 μg/mL. Ficolin-2 and ficolin-3 are expressed in the liver and are secreted into the serum. Two cases of ficolin-3 deficiency due to homozygosity for a FCN3 frameshift mutation (c.349delC, rs28357092) lacking the entire fibrinogen-like in exon 5 leading to the abnormal ficolin-3 lacking the entire fibrinogen-like domain have been reported.