Mannose-Binding Lectin: Biologic Characteristics and Role in the Susceptibility to Infections and Ischemia-Reperfusion Related Injury in Critically Ill Neonates

Figure 2

The structural differences due to the variant alleles. Three polymorphisms in the structural gene MBL2, at codons 52, 54, and 57, encode for variant alleles referred to as D, B, and C, respectively; the wild-type gene is A. In the wild type, the correct repetition of Glu-Xaa-Yaa permits the association of three identical polypeptide chains generating the structural subunit. This subunit is stabilized through disulphide bonds in the cross-linking region, with a high-order MBL oligomer formation. The mutations in exon 1 generate three amino acid substitutions in the collagen-like region; two of these substitutions disrupt the Gly-X-Y repeats by exchanging a glycine residue with aspartic acid (variant B) or with glutamine (variant C). A third substitutes a cysteine for an arginine (variant D). These amino acid substitutions disrupt the assembly of the MBL molecule, generating a nonfunctional low-order oligomer formation [15, 46].