title: BcIV, a new paralyzing peptide obtained from the venom of the sea anemone Bunodosoma caissarum. A comparison with the Na+ channel toxin BcIII.
abstract: Sea anemones produce a wide variety of biologically active compounds, such as the proteinaceous neurotoxins and cytolysins. Herein we report a new peptide, purified to homogeneity from the neurotoxic fraction of B. caissarum venom, by using gel filtration followed by rp-HPLC, naming it as BcIV. BcIV is a 41 amino acid peptide (molecular mass of 4669 amu) possessing 6 cysteines covalently linked by three disulfide bonds. This toxin has 45 and 48% of identity when compared to APETx1 and APETx2 from Anthopleura elegantissima, respectively, and 42% of identity with Am-II and BDS-I and-II obtained from Antheopsis maculata and Anemonia sulcata, respectively. This neurotoxin presents only a weak-paralyzing action (minimal Lethal Dose close to 2000 microg/kg) in swimming crabs Callinectes danae. This appears to be a different effect to that caused by the type 1 sea anemone toxin BcIII that is lethal to the same animals at lower doses (LD50=219 microg/kg). Circular dichroism spectra of BcIII and BcIV show a high content of beta-strand secondary structure in both peptides, very similar to type 1 sodium channel toxins from various sea anemones, and to APETx1 and APETx2 from A. elegantissima, a HERG channel modulator and an ASIC3 inhibitor, respectively. Interestingly, BcIII and BcIV have similar effects on the action potential of the crab leg nerves, suggesting the same target in this tissue. As BcIII was previously reported as a Na+ channel effector and BcIV is inactive over Na+ currents of mammalian GH3 cells, we propose a species-specific action for this new molecule. A molecular model of BcIV was constructed using the structure of the APETx1 as template and putative key residues are discussed.
authors.affiliation: Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, Rua do Matão 101, Travessa 14, 05508-900 São Paulo-SP, Brazil. jstolarz@usp.br
authors.forename: Joacir Stolarz
authors.initials: JS
authors.lastname: Oliveira
authors.forename: André Junqueira
authors.initials: AJ
authors.lastname: Zaharenko
authors.forename: Wilson Alves
authors.initials: WA
authors.lastname: Ferreira
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Konno
authors.forename: Cláudio Saburo
authors.initials: CS
authors.lastname: Shida
authors.forename: Michael
authors.initials: M
authors.lastname: Richardson
authors.forename: Aline Duarte
authors.initials: AD
authors.lastname: Lúcio
authors.forename: Paulo Sérgio Lacerda
authors.initials: PS
authors.lastname: Beirão
authors.forename: José Carlos
authors.initials: JC
authors.lastname: de Freitas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001681:Biological Assay; D003386:Brachyura / Q000187:drug effects; D002942:Circular Dichroism; D003064:Cnidarian Venoms / Q000737:chemistry* / Q000633:toxicity; D004594:Electrophysiology; D007928:Lethal Dose 50; D008387:Marine Toxins / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity*; D010243:Paralysis / Q000139:chemically induced; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity; D012615:Sea Anemones / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects*
chemical_list: C515745:BcIV peptide, Bunodosoma caissarum; D003064:Cnidarian Venoms; D008387:Marine Toxins; D009498:Neurotoxins; D010455:Peptides; D015222:Sodium Channels; C083402:anemone toxin BcIII (Bunodosoma caissarum)