Abstract
CEL-III is a hemolytic lectin isolated from the sea cucumber Cucumaria echinata. This lectin is composed of two carbohydrate-binding domains (domains 1 and 2) and one oligomerization domain (domain 3). After binding to the cell surface carbohydrate chains through domains 1 and 2, domain 3 self-associates to form transmembrane pores, leading to cell lysis or death, which resembles other pore-forming toxins of diverse organisms. To elucidate the pore formation mechanism of CEL-III, the crystal structure of the CEL-III oligomer was determined. The CEL-III oligomer has a heptameric structure with a long β-barrel as a transmembrane pore. This β-barrel is composed of 14 β-strands resulting from a large structural transition of α-helices accommodated in the interface between domains 1 and 2 and domain 3 in the monomeric structure, suggesting that the dissociation of these α-helices triggered their structural transition into a β-barrel. After heptamerization, domains 1 and 2 form a flat ring, in which all carbohydrate-binding sites remain bound to cell surface carbohydrate chains, stabilizing the transmembrane β-barrel in a position perpendicular to the plane of the lipid bilayer.
Highlights
The hemolytic lectin CEL-III self-oligomerizes upon binding to cell surface carbohydrates to form transmembrane pores
Structural changes that occur during pore formation in target cell membranes. Their pore formation processes proceed through binding to the cell membrane and self-association to form heptamers or octamers, followed by conformational changes to form a transmembrane -barrel. Both monomeric and oligomeric structures are available for ␥-hemolysin, which enables a detailed examination of structural changes during pore formation, there is a paucity of information for other pore-forming toxins (PFTs) that are postulated to undergo large conformational changes on the cell membrane, leading to the formation of the membrane-inserted oligomers
CEL-III is a eukaryotic PFT that has been purified as a Ca2ϩdependent hemolytic lectin from the marine invertebrate Cucumaria echinata [5,6,7]
Summary
The hemolytic lectin CEL-III self-oligomerizes upon binding to cell surface carbohydrates to form transmembrane pores. Their pore formation processes proceed through binding to the cell membrane and self-association to form heptamers or octamers, followed by conformational changes to form a transmembrane -barrel Both monomeric and oligomeric structures are available for ␥-hemolysin, which enables a detailed examination of structural changes during pore formation, there is a paucity of information for other PFTs that are postulated to undergo large conformational changes on the cell membrane, leading to the formation of the membrane-inserted oligomers. CEL-III is a eukaryotic PFT that has been purified as a Ca2ϩdependent hemolytic lectin from the marine invertebrate Cucumaria echinata (sea cucumber) [5,6,7] This lectin exhibits binding affinity for carbohydrates containing GalNAc and Gal at nonreducing ends, it shows hemolytic and cytotoxic activities by forming pores in target cell membrane, which may contribute to defense against this animal’s predators. Compared with the monomeric structure, an extensive secondary structural change of ␣-helices to -strands is suggested to play an important role in the pore formation process in target cell membrane
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
