title: Hemolytic lectin CEL-III heptamerizes via a large structural transition from α-helices to a β-barrel during the transmembrane pore formation process.
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.
authors.affiliation: From the Laboratory of Biomolecular Chemistry, Graduate School of Engineering, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Unno
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Goda
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Hatakeyama
mesh_terms: D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D018360:Crystallography, X-Ray; D048016:Cucumaria / Q000378:metabolism; D006461:Hemolysis; D037102:Lectins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction
chemical_list: C402644:CEL-III lectin, Cucumaria echinata; D037102:Lectins
keywords: Carbohydrate; Hemolysin; Lectin; Membrane; Oligomer; Pore-forming Toxin; Toxins; X-ray Crystallography; β-Barrel