Neurotoxin B-IV

Neurotoxin B-IV is a venom peptide secreted by a large marine worm called Cerebratulus lacteus that inhabits the northeastern coast of North America. This neurotoxin belongs to a major type of B polypeptide neurotoxins, which appear to be selectively toxic for crustaceans. The mode of action for neurotoxin B-IV has not been clearly established. However, it is likely that B neurotoxins prolong the repolarization phase of action potentials by interacting with voltage-gated sodium channels.

Etymology and Source

Neurotoxin B-IV is found in the mucus secretions of the Atlantic coast marine worm Cerebratulus lacteus.^[1] Cerebratulus lacteus produces two major types of polypeptide neurotoxins namely A and B. Toxins B include four neurotoxins designated B-I to B-IV.^[2][3]

Chemistry

Structure

Neurotoxin B-IV has a helical structure that looks like a hairpin, and consists of 55 amino acid residues, cross-linked by four disulfide bonds. Its molecular size is about 6000 Dalton.^[4] The sequence of the neurotoxin B-IV is ASATWGAAYPACENNCRKKYDLCIRCQGKWAGKRGKCAAHCIIQKNNCKGKCKKE.^[5]

Homology

The complete structures for two of the four B toxins (B-II and B-IV) have been determined.^[5] Toxin B-II differs from B-IV in that the secondary structure of Toxin B-II contains about 15-20% less α-helixes than B-IV due to the differences in the primary structure of the two proteins; amino acids Ala in position 3, Ala in position 7 and Ala in position 8 in B-IV are substituted by amino acids Ser, Gly and Ser in B-II respectively.^[1]

No homology is displayed with other sodium channel selective toxins, such as scorpion and sea anemone venom toxins, despite being similar in size, basicity, and degree of cross-linking. The secondary structures of scorpion and anemone toxins are largely organized into β-sheet conformations, while the secondary structures of B toxins organize in α-helical conformations.^[6]

Family

Neurotoxin B-IV belongs to a family of four homologous polypeptide neurotoxins designated B-I to B-IV which are produced by the marine worm Cerebratulus lacteus.^[2]

Target

Neurotoxin B-IV displays a high affinity binding to a single class of receptor sites on crustacean axon membrane vesicles. B-IV binds to a nerve membrane protein in crustaceans which is similar in size to the β-subunit of sodium channels in nerve and muscle of mammals. The binding site for toxin B-IV is distinct from sodium channel site III, which is targeted by both scorpion and sea anemone toxins.^[2]

Mode of Action

Neurotoxin B-IV appears to prolong the repolarization phase of the action potential in crustacean nerve sodium channels but does not affect the initial opening of these channels.^[3] It is likely that this neurotoxin causes a small depolarization of the resting potential in lobster and crayfish walking leg nerve.^[2]

Cationic residues are important determinants for polypeptide neurotoxins' function. Specifically, the arginine residues, located within the N-terminal helix, seem to be essential for the activity of neurotoxin B-IV and are most likely directly involved in binding.^[2]

Toxicity

Neurotoxin B-IV is selectively toxic to crustaceans inducing paralysis, at mean concentrations of about 20 ng/g of body weight.^[2] This neurotoxin is the most abundant of the B neurotoxin family ^[3] and 15-20-fold less toxic than neurotoxin B-II.^[1]

References

0.00 (0 votes) Original source: https://en.wikipedia.org/wiki/Neurotoxin B-IV. Read more