Structural Analysis of theLaetiporus sulphureusHemolytic Pore-forming Lectin in Complex with Sugars

José M. Mancheño, Hiroaki Tateno, Irwin J. Goldstein, Martín Martínez-Ripoll, Juan A. Hermoso
2005 Journal of Biological Chemistry  
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-Å 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
more » ... tinct modules: an N-terminal lectin module and a pore-forming module. The lectin module has a ␤-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 ␤-pore-forming toxin aerolysin from the Gram-negative bacterium Aeromonas hydrophila, and domains 2 and 3 from the ⑀-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.
doi:10.1074/jbc.m413933200 pmid:15687495 fatcat:7ykddlwa6zdb7envow3ywws5om