MBL binds to repetitive carbohydrate structures on the surfaces of viruses, bacteria, fungi, and protozoa Activation of MBL PathwayStep6807 PathwayStep6808 Lectin pathway of complement activation Authored: de Bono, B, 2004-08-04 09:17:50 GENE ONTOLOGYGO:0001867 Mannose-binding lectin (MBL), a Ca-dependent (C-type) lectin, initiates the complement cascade after binding to specific carbohydrate patterns on pathogenic cell surfaces. The MBL polypeptide chain consists of a short N-terminal cysteine-rich region, a collagen-like region comprising 19 Gly-X-Y triplets, a 34-residue hydrophobic stretch, and a C-terminal C-type lectin domain. MBL monomers associate via their cysteine-rich and collagen-like regions to form homotrimers, and these in turn associate into oligomers. The predominant oligomers found in human serum contain three (MBL-I) or four (MBL-II) homotrimers (Fujita et al. 2004; Teillet et al. 2005). These oligomers are associated with homodimers of the MASP2 serine protease (Fujita et al. 2004; Hajela et al. 2002). MBL-II is associated with one or two MASP homodimers (Chen and Wallis 2001, 2004). The carbohydrate recognition domain (CRD) of MBL binds carbohydrates with 3- and 4- OH groups in the pyranose ring, such as mannose and N-acetyl-D-glucosamine, in the presence of Ca2+. This binding results in a change in conformation of the MBL and activation of MASP by cleavage (Fujita et al. 2004). MASP2a cleaves C4 to generate C4a and C4b. C4b binds to the bacterial or foreign cell surface via its thioester bond (Law and Dodds 1997) and binds circulating C2. Bound C2 is then cleaved by MASP2 to yield the C3 convertase C4b-C2a. MASP1, a serine protease encoded by an alternatively spliced transcript of the same gene that encodes MASP2, can also be activated by binding of the MBL complex to carbohydrate patterns. MASP-1a cleaves fibrinogen to yield fibrinopeptide B, and cleaves and activates factor XIII. While MASP1 can also cleave C2, it is not thought to mediate the initial cleavage and activation of C2 in vivo (Chen and Wallis 2004). MASP-1a may have a role in cleavage of 'dead C3', i.e. C3(H2O) (Hajela et al. 2002). Pubmed11337510 Pubmed11532276 Pubmed12396008 Pubmed15060079 Pubmed15199963 Pubmed15728497 Pubmed9041627 Reactome Database ID Release 43166662 Reactome, http://www.reactome.org ReactomeREACT_7964 Reviewed: D'Eustachio, P, 2006-07-03 21:35:13