Dendrotoxin

Dendrotoxins are a class of presynaptic neurotoxins produced by mamba snakes (Dendroaspis) that block particular subtypes of voltage-gated potassium channels in neurons, thereby enhancing the release of acetylcholine at neuromuscular junctions. Because of their high potency and selectivity for potassium channels, dendrotoxins have proven to be extremely useful as pharmacological tools for studying the structure and function of these ion channel proteins. Dendrotoxins have been shown to block particular subtypes of voltage-gated potassium (K+) channels in neuronal tissue. In the nervous system, voltage-gated K+ channels control the excitability of nerves and muscles by controlling the resting membrane potential and by repolarizing the membrane during action potentials. Dendrotoxin has been shown to bind the nodes of Ranvier of motor neurons and to block the activity of these potassium channels. In this way, dendrotoxins prolong the duration of action potentials and increase acetylcholine release at the neuromuscular junction, which may result in muscle hyperexcitability and convulsive symptoms. Dendrotoxins are ~7kDa proteins consisting of a single peptide chain of approximately 57-60 amino acids. Several homologues of alpha-dendrotoxin have been isolated, all possessing a slightly different sequence. However, the molecular architecture and folding conformation of these proteins are all very similar. Dendrotoxins possess a very short 310-helix near the N-terminus of the peptide, while a two turn alpha-helix occurs near the C-terminus. A two-stranded antiparallel β-sheet occupies the central part of the molecular structure. These two β-strands are connected by a distorted β-turn region that is thought to be important for the binding activity of the protein. All dendrotoxins are cross-linked by three disulfide bridges, which add stability to the protein and greatly contribute to its structural conformation. The cysteine residues forming these disulfide bonds have been conserved among all members of the dendrotoxin family, and are located at C7-C57, C16-C40, and C32-C53 (numbering according to alpha-dendrotoxin).