Structure and pharmacology of spider venom neurotoxins

Spider venoms are complex mixtures of neurotoxic peptides, proteins and low molecular mass organic molecules. Their neurotoxic activity is due to the interaction of the venom components with cellular receptors, in particular ion channels. Spider venoms have proven to be a rich source of highly speci fic peptide ligands for selected subtypes of potassium, sodium and calcium channels, and these toxins have been used to elucidate the structure and ph ysiological roles of the channels in excitable and non-excitable cells. Spi der peptides show great variability in their pharmacological activity and p rimary structure but relative homogeneity in their secondary structure. Fol lowing diverse molecular evolution mechanisms, and in particular selective hypermutation, short spider peptides appear to have functionally diversifie d while retaining a conserved molecular scaffold. This paper reviews the co mposition and pharmacology of spider venoms with emphasis on polypeptide to xin structure, mode of action and molecular evolution. (C) 2000 societe fra ncaise de biochimie et biologie moleculaire / Editions scientifiques et med icales Elsevier SAS.