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[edit]
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[edit]
Structure[edit]
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[edit]
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[edit]
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[edit]
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[edit]
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[edit]
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[edit]
- ^ a b c Howell M.L., Blumenthal K.M., (1989). Cloning and Expression of a Synthetic Gene for Cerebratulus lacteus Neurotoxin B-IV. Journal of biological chemistry. 264 (26): 15268-15273.
- ^ a b c d e f Wen P.H., Blumenthal K.M., (1996). Role of Electrostatic Interactions in Defining the Potency of Neurotoxin B-IV from Cerebratulus lacteus. Journal of biological chemistry. 271 (47): 29752-29758. doi: 10.1074/jbc.271.47.29752.
- ^ a b c Blumenthal, K. M., Kem, W. R., (1976). Structure and action of heteronemertine polypeptide toxins. Primary structure of Cerebratulus lacteus toxin B-IV. Journal of Biological Chemistry. 251(19): 6025-6029.
- ^ Kem W.R., (2013). Worm Peptides. Handbook of Biologically Active Peptides: chpt. 65 p. 483-487. doi: https://doi.org/10.1016/B978-0-12-385095-9.00065-8.
- ^ a b Barnham, K.J., Dyke, T.R., Kem, W.R., Norton, R.S., (1997). Structure of Neurotoxin B-IV from the Marine Worm Cerebratulus lacteus: a Helical Hairpin Cross-linked by Disulphide bonding. J. Mol. Biol. 268(5): 886±902. doi: 10.1006/jmbi.1997.0980.
- ^ Howell, M. L., Blumenthal, K. M. (1991). Mutagenesis of Cerebratulus lacteus neurotoxin B-IV identifies NH2-terminal sequences important for biological activity. Journal of Biological Chemistry, 266(20), 12884-12888.