title: Structural analysis of the Laetiporus sulphureus hemolytic pore-forming lectin in complex with sugars.
abstract: LSL is a lectin produced by the parasitic mushroom Laetiporus sulphureus, which exhibits hemolytic and hemagglutinating activities. Here, we report the crystal structure of LSL refined to 2.6-A resolution determined by the single isomorphous replacement method with the anomalous scatter (SIRAS) signal of a platinum derivative. The structure reveals that LSL is hexameric, which was also shown by analytical ultracentrifugation. The monomeric protein (35 kDa) consists of two distinct modules: an N-terminal lectin module and a pore-forming module. The lectin module has a beta-trefoil scaffold that bears structural similarities to those present in toxins known to interact with galactose-related carbohydrates such as the hemagglutinin component (HA1) of the progenitor toxin from Clostridium botulinum, abrin, and ricin. On the other hand, the C-terminal pore-forming module (composed of domains 2 and 3) exhibits three-dimensional structural resemblances with domains 3 and 4 of the beta-pore-forming toxin aerolysin from the Gram-negative bacterium Aeromonas hydrophila, and domains 2 and 3 from the epsilon-toxin from Clostridium perfringens. This finding reveals the existence of common structural elements within the aerolysin-like family of toxins that could be directly involved in membrane-pore formation. The crystal structures of the complexes of LSL with lactose and N-acetyllactosamine reveal two dissacharide-binding sites per subunit and permits the identification of critical residues involved in sugar binding.
authors.affiliation: Grupo de Cristalografía Macromolecular y Biología Estructural, Instituto Rocasolano, CSIC, Serrano, 119, 28006 Madrid, Spain. xjosemi@iqfr.csic.es
authors.forename: José M
authors.initials: JM
authors.lastname: Mancheño
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tateno
authors.forename: Irwin J
authors.initials: IJ
authors.lastname: Goldstein
authors.forename: Martín
authors.initials: M
authors.lastname: Martínez-Ripoll
authors.forename: Juan A
authors.initials: JA
authors.lastname: Hermoso
mesh_terms: D000036:Abrin / Q000737:chemistry; D016980:Aeromonas hydrophila / Q000378:metabolism; D000363:Agaricales / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000606:Amino Sugars / Q000737:chemistry; D001665:Binding Sites; D002241:Carbohydrates / Q000737:chemistry*; D003014:Clostridium botulinum / Q000378:metabolism; D003016:Clostridium perfringens / Q000378:metabolism; D018360:Crystallography, X-Ray; D004187:Disaccharides / Q000737:chemistry; D005690:Galactose / Q000737:chemistry; D007785:Lactose / Q000737:chemistry; D037102:Lectins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010984:Platinum / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012276:Ricin / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D014461:Ultracentrifugation
chemical_list: D000606:Amino Sugars; D002241:Carbohydrates; D004187:Disaccharides; D037102:Lectins; D000036:Abrin; C000458:N-acetyllactosamine; D010984:Platinum; D012276:Ricin; D007785:Lactose; D005690:Galactose