Dendrotoxins: How Does Structure Determine Function?

Dendrotoxins are a family of small proteins isolated from mamba (Dendroaspis) snake venoms. The toxins contain 57-60 amino acid residues cross-linked by three disulphide bridges. They are homologous to Kunitz-type serine proteinase inhibitors, such as aprotinin, (BPTI) although they have little anti-proteinase activity. The dendrotoxins block some subtypes of voltage-dependent potassium channels in neurones. Studies with cloned K+ channels indicate that alpha-dendrotoxin from green mamba Dendroaspis angusticeps blocks Kv1.1, Kv1.2 and Kv1.6 channels in the nanomolar range. Engineered and modified versions of dendrotoxin are being investigated to define the interactive site and account for differences in K+ channel selectivity.