Structure-function relationships for cardiotoxins interacting with phospholipids.
Four cardiotoxins (CTX I-IV) from Naja mossambica mossambica were compared for their ability to interact with phospholipid vesicles and their capacity to bind erythrocytes. It is concluded that the affinity of the toxins always increases in the order: I approximately equal to II less than III less than IV. The binding is specific for charged lipids even in lipid mixtures. Proteolytic attack of the free and lipid-bound cardiotoxin indicates that at least the first loop Leu1-Thr13 is at the lipid contact. Tryptic and synthetic peptides constitutive of this loop are shown to interact with lipids. Arg5 residue increases the affinity toward the bilayer. The Raman spectra of lipid-bound cardiotoxin indicate a secondary and tertiary structure mainly similar to that of the free toxin. On charged lipids cardiotoxins induce a decrease of the enthalpy and an increase of disorder without change in the transition temperature; at saturating amounts of toxin the transition is abolished. In binary mixtures of phosphatidylcholine and charged lipids the observed effects can be accounted by a phase separation induced by the toxin.
D000595:Amino Acid Sequence; D004179:Cobra Cardiotoxin Proteins; D004546:Elapid Venoms; D004910:Erythrocyte Membrane / Q000378:metabolism; D007700:Kinetics; D008081:Liposomes; D009498:Neurotoxins; D010743:Phospholipids; D013050:Spectrometry, Fluorescence
D004179:Cobra Cardiotoxin Proteins; D004546:Elapid Venoms; D008081:Liposomes; D009498:Neurotoxins; D010743:Phospholipids