1.C.100 The Thermostable Direct Hemolysin (TDH) Family
Thermostable direct hemolysin (TDH) is a major virulence factor of Vibrio parahaemolyticus that causes pandemic foodborne enterocolitis mediated by seafood. TDH is a tetramer in solution and possesses extreme hemolytic activity. Yanagihara et al. (2010) presented the crystal structure of the TDH tetramer at 1.5 A resolution. It forms a central pore with dimensions of 23 A in diameter and approximately 50 A in depth. Pi-cation interactions between protomers comprising the tetramer were indispensable for hemolytic activity. The N-terminal region was intrinsically disordered outside of the pore. Molecular dynamic simulations suggested that water molecules permeate freely through the central and side channel pores. Electron micrographs showed that TDH attached to liposomes. These findings imply a novel membrane attachment mechanism by a soluble tetrameric pore-forming toxin.
TDH and TDH-related hemolysin (TRH) are major virulence factors of Vibrio parahaemolyticus. The crystal structure of the TDH tetramer with a central channel is known. Ohnishi et al. (2011) described the biophysical properties of TRH, which displays 67% amino acid similarity with TDH. Molecular modeling provided a good fit of the overall structure of TDH and TRH. TRH formed tetramer in solution. These toxins showed hemolytic activity on red blood cells. Their 3-d structures reveal a β-sandwich domain similar to actinoporins plus a C-terminal region linked to the barrel via a disulfide bond (Kundu et al. 2016).