Diversity of folds in animal toxins acting on ion channels

Mouhat, Stéphanie; Jouirou, Besma; Mosbah, Ahmed; Waard, Michel De; Sabatier, Jean‐Marc

doi:10.1042/bj20031860

Cited by 227 publications

(178 citation statements)

References 61 publications

(100 reference statements)

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“…The mechanisms underlying the blockade of voltage-gated K ϩ channels by ␣-KTx toxins have been intensively explored in the last decade (11,(43)(44)(45) by the modeling analysis of the toxin-K ϩ channel complex generated by docking and dynamic simulations. In order to elucidate the possible interaction mode, the three-dimensional structural model of the BmP09-BK channel complex was generated by docking and dynamic simulations (Fig.…”

Section: The Possible Interaction Mode Of Bmp09 With Bk Channel-mentioning

confidence: 99%

BmP09, a “Long Chain” Scorpion Peptide Blocker of BK Channels

Yao

Chen

et al. 2005

Journal of Biological Chemistry

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A novel "long chain" toxin BmP09 has been purified and characterized from the venom of the Chinese scorpion Buthus martensi Karsch. The toxin BmP09 is composed of 66 amino acid residues, including eight cysteines, with a mass of 7721.0 Da. Compared with the B. martensi Karsch AS-1 as a Na ؉ channel blocker (7704.8 Da), the BmP09 has an exclusive difference in sequence by an oxidative modification at the C terminus. The sulfoxide Met-66 at the C terminus brought the peptide a dramatic switch from a Na ؉ channel blocker to a K ؉ channel blocker. Upon probing the targets of the toxin BmP09 on the isolated mouse adrenal medulla chromaffin cells, where a variety of ion channels coexists, we found that the toxin BmP09 specifically blocked large conductance Ca 2؉ -and voltage-dependent K ؉ channels (BK) but not Na ؉ channels at a range of 100 nM concentration. This was further confirmed by blocking directly the BK channels encoded with mSlo1 ␣-subunits in Xenopus oocytes. The half-maximum concentration EC 50 of BmP09 was 27 nM, and the Hill coefficient was 1.8. In outside-out patches, the 100 nM BmP09 reduced ϳ70% currents of BK channels without affecting the single-channel conductance. In comparison with the "short chain" scorpion peptide toxins such as Charybdotoxin, the toxin BmP09 behaves much better in specificity and reversibility, and thus it will be a more efficient tool for studying BK channels. A three-dimensional simulation between a BmP09 toxin and an mSlo channel shows that the Lys-41 in BmP09 lies at the center of the interface and plugs into the entrance of the channel pore. The stable binding between the toxin BmP09 and the BK channel is favored by aromatic -interactions around the center.

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Section: The Possible Interaction Mode Of Bmp09 With Bk Channel-mentioning

confidence: 99%

BmP09, a “Long Chain” Scorpion Peptide Blocker of BK Channels

Yao

Chen

et al. 2005

Journal of Biological Chemistry

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“…2b) (Cotton et al 1997;Dauplais et al 1997;Gendeh et al 1997b;Tudor et al 1996). Two-dimensional 1 H NMR studies have shown that the SAK-I toxins secondary structure is mainly characterized by two short α-helices without β-sheet and belongs to the αα-type of fold (Dauplais et al 1997;Mouhat et al 2004;Tudor et al 1996). These toxins do not share structure homologies in sequence and disulfide pairings with scorpion (e.g.…”

Section: Sea Anemone K + Channel Toxin Structuresmentioning

confidence: 99%

“…Only two other peptides are known to block ERG type channels: ErgTx1 and BeKm-1, two scorpion toxins isolated from Centruroides noxius and Buthus eupeus venoms, respectively. These scorpion toxins belong to the Csαβ fold family characterized by a α-helix linked by disulfide bridges to a triple-stranded β-sheet (Bontems et al 1991;Mouhat et al 2004). ErgTx1 and BeKm display different species-specific effects and affinities for the three neuronal members of ERG channel Kv3.1 Kv3.2 Kv3.3 Kv3.4 Fig.…”

Section: Effect Of Sak-iii Toxins On Different Subfamilies Of Kv Chanmentioning

confidence: 99%

Developmental Biology of Neoplastic Growth

Macieira‐Coelho¹

2005

Progress in Molecular and Subcellular Biology

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“…[71][72] Such type of fold is found in the classes of human -defensins ( Figure 3) and scorpion toxins that target Na + -channels. 73 Thus crotamine shares the functional properties of cell penetration with most CPPs and the structural characteristics with the classes of both membrane-active peptides: AMPs and CPPs. However, any antimicrobial activity was yet attributed to crotamine.…”

Section: Cell Penetrating Peptides and Crotaminementioning

confidence: 99%

Membrane-translocating peptides and toxins: from nature to bedside

Baptista¹,

Kerkis

Silva³

et al. 2008

J. Braz. Chem. Soc.

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Atualmente, diferentes classes funcionais de peptídeos e toxinas biologicamente ativas isolados de diversos organismos são conhecidas. Em medicina, esses polipeptídios podem ser diretamente utilizados ou podem servir como modelos para a geração de moléculas derivadas. Aqui, nós fazemos referência a três classes de peptídeos e toxinas que agem sobre membranas celulares ou sobre sistemas de transporte por membranas: (i) toxinas binárias; (ii) peptídeos antimicrobianos; (iii) peptídeos penetradores de células. As toxinas binárias têm sido geneticamente manipuladas para gerar imunotoxinas específicas, enquanto os peptídeos antimicrobianos são usados como agentes alternativos contra células tumorais e microbianas resistentes. Os peptídeos penetradores de células têm aplicações que vão desde a transfecção celular quanto ao transporte intracelular de nanopartículas. Nosso grupo vem investigando a capacidade da crotamina, um peptídeo do veneno de cascavel, em translocar membranas celulares, bem como de utilizar a crotamina como sistema de transporte molecular e de análise de imagens.Today, different functional classes of bioactive peptides and toxins isolated from diverse sources of living organisms are known. In medicine, these polypeptides present the potential to be used structurally unmodified or to serve as templates for molecular design of improved derivatives. Here, we refer to members of three classes of remarkable peptides and toxins that act at the cell membranes level and membrane trafficking systems: (i) the binary toxins (ii) the antimicrobial peptides and (iii) the cell penetrating peptides. Binary toxins have been genetically manipulated to generate specific immunotoxins, while antimicrobial peptides are in use as alternative agents against resistant microbes and tumor cells. Cell penetrating peptides have applications as diverse as cell transfection and transport of nanomaterials. Our group is dissecting the capacity of crotamine, a peptide from rattlesnake venom, to translocate cell membranes and use it as a delivery system in the transducing technology and molecular imaging.Keywords: cytolysin, binary toxin, antimicrobial peptide, cell-penetrating peptide, animal toxin, nanobiotechnology Binary Bacterial ToxinsA wide variety of bacterial toxins that has the cell membrane as a target is presently known. Indeed the molecular diversity of bacterial toxins is so remarkable that a large number of microorganisms secret several toxic peptides and polypeptides devoid of or having catalytic activity. All these toxins are capable of intoxicating eucaryotic cells by interfering directly with cytoplasmic membrane or by using membrane systems to gain access Membrane-translocating Peptides and Toxins: from Nature to Bedside J. Braz. Chem. Soc. 212 to the interior of cells for the delivery of their active domain.In the first case, single chain proteins or composed of two separate water-soluble proteins -which oligomerize during their action on phospholipid membrane and form pores or channels -encompass the cytoly...

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Diversity of folds in animal toxins acting on ion channels

Cited by 227 publications

References 61 publications

BmP09, a “Long Chain” Scorpion Peptide Blocker of BK Channels

BmP09, a “Long Chain” Scorpion Peptide Blocker of BK Channels

Developmental Biology of Neoplastic Growth

Membrane-translocating peptides and toxins: from nature to bedside

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