1.C.96 The Haemolytic Lectin, CEL-III (CEL-III) Family
CEL-III is an oligomeric haemolytic lectin, which has two beta-trefoil domains (domains 1 and 2) and a beta-sheet-rich domain (domain 3). In domain 3 (residues 284-432), there is a hydrophobic region containing two alpha-helices (H8 and H9, residues 317-357) and a loop between them, in which alternate hydrophobic residues, especially Val residues, are present. To elucidate the role of the alpha-helix region in the haemolytic process, peptides corresponding to different parts of this region were synthesized and characterized (Hisamatsu et al., 2008). The peptides containing the sequence that corresponded to the loop and second alpha-helix (H9) showed the strongest antibacterial activity for Staphylococcus aureus and Bacillus subtilis through a marked permeabilization of the bacterial cell membrane. Replacement of Lys405 in domain 3 of CEL-III by smaller residues led to a marked increase in hemolytic activity, suggesting that moderately destabilizing domain 3 facilitates formation of transmembrane pores through conformational changes (Nagao et al. 2016).
CEL-III is a Ca2+-dependent, galactose-specific lectin from the sea cucumber, Cucumaria echinata, which exhibits hemolytic and hemagglutinating activities. Six molecules of CEL-III oligomerize to form an ion-permeable pore in the cell membrane (Uchida et al. 2004). The crystal structure of CELIII at 1.7 A resolution revealed three distinct domains: two N-terminal two carbohydrate-binding domains (1 and 2), which adopt beta-trefoil folds such as the B-chain of ricin and are members of the (QXW)(3) motif family; and domain 3, which has a fold composed of two alpha-helices and one beta-sandwich. CEL-III binds five Ca2+ ions at five of the six subdomains in both domains 1 and 2. These domains may rearrange upon carbohydrate binding in the erythrocyte membrane and be responsible for oligomerization and hemolysis (Uchida et al. 2004).
The generalized transport reaction catalyzed by CEL-III is:
Molecules (in) → Molecules (out)