BcIV, a new paralyzing peptide obtained from the venom of the sea anemone Bunodosoma caissarum. A comparison with the Na+ channel toxin BcIII.
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.
Oliveira
Joacir Stolarz
JS
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
Zaharenko
André Junqueira
AJ
Ferreira
Wilson Alves
WA
Konno
Katsuhiro
K
Shida
Cláudio Saburo
CS
Richardson
Michael
M
Lúcio
Aline Duarte
AD
Beirão
Paulo Sérgio Lacerda
PS
de Freitas
José Carlos
JC
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*
C515745:BcIV peptide, Bunodosoma caissarum; D003064:Cnidarian Venoms; D008387:Marine Toxins; D009498:Neurotoxins; D010455:Peptides; D015222:Sodium Channels; C083402:anemone toxin BcIII (Bunodosoma caissarum)