BcsTx3 is a founder of a novel sea anemone toxin family of potassium channel blocker

Diego J.B. Orts; Yehu Moran; Camila T. Cologna; Steve Peigneur; Bruno Madio; Daniela Praher; Loic Quinton; Edwin De Pauw; José E.P.W. Bicudo; Jan Tytgat; José C. De Freitas

doi:10.1111/febs.12456

BcsTx3 is a founder of a novel sea anemone toxin family of potassium channel blocker

Diego J.B. Orts^*, Yehu Moran, Camila T. Cologna, Steve Peigneur, Bruno Madio, Daniela Praher, Loic Quinton, Edwin De Pauw, José E.P.W. Bicudo, Jan Tytgat, José C. De Freitas

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

44 Scopus citations

Abstract

Sea anemone venoms have become a rich source of peptide toxins which are invaluable tools for studying the structure and functions of ion channels. In this work, BcsTx3, a toxin found in the venom of a Bunodosoma caissarum (population captured at the Saint Peter and Saint Paul Archipelago, Brazil) was purified and biochemically and pharmacologically characterized. The pharmacological effects were studied on 12 different subtypes of voltage-gated potassium channels (K_V1.1-K_V1.6; K_V2.1; K_V3.1; K_V4.2; K_V4.3; hERG and Shaker IR) and three cloned voltage-gated sodium channel isoforms (Na_V1.2, Na_V1.4 and BgNa_V1.1) expressed in Xenopus laevis oocytes. BcsTx3 shows a high affinity for Drosophila Shaker IR channels over rKv1.2, hKv1.3 and rKv1.6, and is not active on Na_V channels. Biochemical characterization reveals that BcsTx3 is a 50 amino acid peptide crosslinked by four disulfide bridges, and sequence comparison allowed BcsTx3 to be classified as a novel type of sea anemone toxin acting on K_V channels. Moreover, putative toxins homologous to BcsTx3 from two additional actiniarian species suggest an ancient origin of this newly discovered toxin family. We have demonstrated the biochemical and pharmacological characterization of a novel type of sea anemone K_V-toxins. BcsTx3 is a peptidyl toxin with a unique sequence that acts potently upon Shaker IR channels through a pore blocking mechanism. Moreover, the distribution of this newly discovered type of K_V-toxins among different actiniarian species suggests an ancient origin.

Original language	English
Pages (from-to)	4839-4852
Number of pages	14
Journal	FEBS Journal
Volume	280
Issue number	19
DOIs	https://doi.org/10.1111/febs.12456
State	Published - Oct 2013
Externally published	Yes

Keywords

Bunodosoma caissarum
Saint Peter and Saint Paul Archipelago
potassium channel toxin
sea anemone
sequence alignment

Access to Document

10.1111/febs.12456

Cite this

@article{8d016b0bb08e41b490d23b43211ab0d7,

title = "BcsTx3 is a founder of a novel sea anemone toxin family of potassium channel blocker",

abstract = "Sea anemone venoms have become a rich source of peptide toxins which are invaluable tools for studying the structure and functions of ion channels. In this work, BcsTx3, a toxin found in the venom of a Bunodosoma caissarum (population captured at the Saint Peter and Saint Paul Archipelago, Brazil) was purified and biochemically and pharmacologically characterized. The pharmacological effects were studied on 12 different subtypes of voltage-gated potassium channels (KV1.1-KV1.6; KV2.1; KV3.1; KV4.2; KV4.3; hERG and Shaker IR) and three cloned voltage-gated sodium channel isoforms (NaV1.2, NaV1.4 and BgNaV1.1) expressed in Xenopus laevis oocytes. BcsTx3 shows a high affinity for Drosophila Shaker IR channels over rKv1.2, hKv1.3 and rKv1.6, and is not active on NaV channels. Biochemical characterization reveals that BcsTx3 is a 50 amino acid peptide crosslinked by four disulfide bridges, and sequence comparison allowed BcsTx3 to be classified as a novel type of sea anemone toxin acting on KV channels. Moreover, putative toxins homologous to BcsTx3 from two additional actiniarian species suggest an ancient origin of this newly discovered toxin family. We have demonstrated the biochemical and pharmacological characterization of a novel type of sea anemone KV-toxins. BcsTx3 is a peptidyl toxin with a unique sequence that acts potently upon Shaker IR channels through a pore blocking mechanism. Moreover, the distribution of this newly discovered type of KV-toxins among different actiniarian species suggests an ancient origin.",

keywords = "Bunodosoma caissarum, Saint Peter and Saint Paul Archipelago, potassium channel toxin, sea anemone, sequence alignment",

author = "Orts, {Diego J.B.} and Yehu Moran and Cologna, {Camila T.} and Steve Peigneur and Bruno Madio and Daniela Praher and Loic Quinton and {De Pauw}, Edwin and Bicudo, {Jos{\'e} E.P.W.} and Jan Tytgat and {De Freitas}, {Jos{\'e} C.}",

year = "2013",

month = oct,

doi = "10.1111/febs.12456",

language = "אנגלית",

volume = "280",

pages = "4839--4852",

journal = "FEBS Journal",

issn = "1742-464X",

publisher = "John Wiley and Sons Inc.",

number = "19",

}

TY - JOUR

T1 - BcsTx3 is a founder of a novel sea anemone toxin family of potassium channel blocker

AU - Orts, Diego J.B.

AU - Moran, Yehu

AU - Cologna, Camila T.

AU - Peigneur, Steve

AU - Madio, Bruno

AU - Praher, Daniela

AU - Quinton, Loic

AU - De Pauw, Edwin

AU - Bicudo, José E.P.W.

AU - Tytgat, Jan

AU - De Freitas, José C.

PY - 2013/10

Y1 - 2013/10

N2 - Sea anemone venoms have become a rich source of peptide toxins which are invaluable tools for studying the structure and functions of ion channels. In this work, BcsTx3, a toxin found in the venom of a Bunodosoma caissarum (population captured at the Saint Peter and Saint Paul Archipelago, Brazil) was purified and biochemically and pharmacologically characterized. The pharmacological effects were studied on 12 different subtypes of voltage-gated potassium channels (KV1.1-KV1.6; KV2.1; KV3.1; KV4.2; KV4.3; hERG and Shaker IR) and three cloned voltage-gated sodium channel isoforms (NaV1.2, NaV1.4 and BgNaV1.1) expressed in Xenopus laevis oocytes. BcsTx3 shows a high affinity for Drosophila Shaker IR channels over rKv1.2, hKv1.3 and rKv1.6, and is not active on NaV channels. Biochemical characterization reveals that BcsTx3 is a 50 amino acid peptide crosslinked by four disulfide bridges, and sequence comparison allowed BcsTx3 to be classified as a novel type of sea anemone toxin acting on KV channels. Moreover, putative toxins homologous to BcsTx3 from two additional actiniarian species suggest an ancient origin of this newly discovered toxin family. We have demonstrated the biochemical and pharmacological characterization of a novel type of sea anemone KV-toxins. BcsTx3 is a peptidyl toxin with a unique sequence that acts potently upon Shaker IR channels through a pore blocking mechanism. Moreover, the distribution of this newly discovered type of KV-toxins among different actiniarian species suggests an ancient origin.

AB - Sea anemone venoms have become a rich source of peptide toxins which are invaluable tools for studying the structure and functions of ion channels. In this work, BcsTx3, a toxin found in the venom of a Bunodosoma caissarum (population captured at the Saint Peter and Saint Paul Archipelago, Brazil) was purified and biochemically and pharmacologically characterized. The pharmacological effects were studied on 12 different subtypes of voltage-gated potassium channels (KV1.1-KV1.6; KV2.1; KV3.1; KV4.2; KV4.3; hERG and Shaker IR) and three cloned voltage-gated sodium channel isoforms (NaV1.2, NaV1.4 and BgNaV1.1) expressed in Xenopus laevis oocytes. BcsTx3 shows a high affinity for Drosophila Shaker IR channels over rKv1.2, hKv1.3 and rKv1.6, and is not active on NaV channels. Biochemical characterization reveals that BcsTx3 is a 50 amino acid peptide crosslinked by four disulfide bridges, and sequence comparison allowed BcsTx3 to be classified as a novel type of sea anemone toxin acting on KV channels. Moreover, putative toxins homologous to BcsTx3 from two additional actiniarian species suggest an ancient origin of this newly discovered toxin family. We have demonstrated the biochemical and pharmacological characterization of a novel type of sea anemone KV-toxins. BcsTx3 is a peptidyl toxin with a unique sequence that acts potently upon Shaker IR channels through a pore blocking mechanism. Moreover, the distribution of this newly discovered type of KV-toxins among different actiniarian species suggests an ancient origin.

KW - Bunodosoma caissarum

KW - Saint Peter and Saint Paul Archipelago

KW - potassium channel toxin

KW - sea anemone

KW - sequence alignment

UR - http://www.scopus.com/inward/record.url?scp=84884591716&partnerID=8YFLogxK

U2 - 10.1111/febs.12456

DO - 10.1111/febs.12456

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 23895459

AN - SCOPUS:84884591716

SN - 1742-464X

VL - 280

SP - 4839

EP - 4852

JO - FEBS Journal

JF - FEBS Journal

IS - 19

ER -

BcsTx3 is a founder of a novel sea anemone toxin family of potassium channel blocker

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this