Pyrularia Thionin: Physical Properties, Biological Responses and Comparison to Other Thionins and Cardiotoxin

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Abstract
Pyrularia thionin (PT) is a unique thionin which occupies a position between the viscotoxins and Gramineae thionins. Like the viscotoxins, PT comes from a dicotyledonous plant, Pyrularia pubera, and PT has a higher degree of amino acid homology with the viscotoxins than it does with the cereal grain thionins (1). However, PT has 4 disulfide bonds, as do the cereal grain thionins, and the viscotoxins have only 3. PT is distinct from both in that it is monomorphic. All thionins interact with and increase the permeability of cell membranes and are cytotoxic to some degree. PT and cardiotoxins also depolarize cell membranes, and PT opens a Ca2+ channel. PT as well as the other thoinins are amphipathic. This is apparent in the reported three dimensional structure of α-1 purothionin, which clearly shows distinct hydrophilic and hydrophobic domains on the surface of the protein, which contains two helical and one anti-parallel β-pleated sheet region. Examination of the physical properties show that PT combines with acidic phospholipids in synthetic membranes, and shows some specificity for phosphatidylserine. Our thesis is that PT combines with a specific phospholipid domain on the cellular membrane, most likely contining phosphatidylserine, causing early changes in membrane properties, including an increase in order parameter of the phospholipids, an increase in membrane permeability, depolarization of the membrane and opening of a Ca2+ channel. Later membrane responses include blebbing of the membrane bilayer and activation of an endogenous phospholipase A2. The activation of this enzyme results in membrane degradation and is the major cause of the long term cellular responses attributed to the basic peptide, including killing of cells in culture and neurotoxicity to animals. The cause of PT-induced hemolytic activity is not immediately apparent. In its binding properties, physical responses of the membrane and biological responses of cells, cardiotoxin from cobra venom behaves in a very similar manner to PT, indicating a similar mechanism of action for both toxic peptides.