Fibrinogen Type Lectins

Abstract

Ficolins are one of the most important groups of proteins capable of recognizing pathogens, and they function in the innate immune defence as pathogen-associated molecular pattern recognition molecules (Bohlson et al. 2007; Thiel et al. 1997; Runza et al. 2008). Ficolins comprises of a collagen like domain at the N-terminus and a FBG (fibrinogen-like domain), which is the ligand-binding site, at the C-terminus, and they form trimer-based multimers that are N-terminally linked by disulfide bonds (Ohashi and Erickson 2004; Hummelshoj et al. 2007). Three human ficolins (L-, M and H -ficolins) have been characterized. The amino acid sequence homologies between L-ficolin and M-ficolin, and between H-ficolin and either L-ficolin or M-ficolin, are 80% and 48% respectively. These ficolins are associated with the mannose-binding lectin-associated serine protease, and the complexes activate the lectin complement pathway. Interestingly, ficolins collaborate with CRP (C-reactive protein), which is highly up-regulated during the acute-phase response, and the interaction stabilizes CRP binding to bacteria, resulting in the activation of the lectin complement pathway (Ng et al. 2007). In addition to humans, ficolins have been identified in different mammalian species including rodents and pigs, which have two related ficolin genes called A and B and α and β, respectively, orthologous to the human L- and M-ficolin genes, respectively (Endo et al. 2004). To date, H-ficolin has only been identified in humans and the mouse and rat homologues of H-ficolin gene are pseudogenes, which accounts for the absence of the corresponding protein in rodents (Endo et al. 2004).