Amino Acid Sequences of Neurotoxins I and III of the Elapidae Snake <i>Naja mossambica mossambica</i>

Gregoire, J; Rochat, Hervé

doi:10.1111/j.1432-1033.1977.tb11881.x

Cited by 28 publications

(12 citation statements)

References 25 publications

(15 reference statements)

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“…Thus, we set out to identify the primary target of rMmTX2 in GABA-depleted rat brain synaptosomes by carrying out competitive binding experiments with modulators of nAChRs, muscarinic (m)AChRs, GABA A receptors, GlyRs, glutamate receptors (GluRs), and acetylcholinesterase. Given its close structural relation to members of the α-neurotoxin family that bind to nAChRs, we initially investigated whether rMmTX2 competes with snake α-neurotoxins (Nmm I and α-bungarotoxin) (35,36), as well as marine snail α-conotoxins (M1 and IM 1) (37, 38) and a plant toxin (d-tubocurarine) (39) (Fig. 3A).…”

Section: Resultsmentioning

confidence: 99%

MmTX1 and MmTX2 from coral snake venom potently modulate GABA _A receptor activity

Rosso

Schwarz

Diaz-Bustamante

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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GABA A receptors shape synaptic transmission by modulating Cl − conductance across the cell membrane. Remarkably, animal toxins that specifically target GABA A receptors have not been identified. Here, we report the discovery of micrurotoxin1 (MmTX1) and MmTX2, two toxins present in Costa Rican coral snake venom that tightly bind to GABA A receptors at subnanomolar concentrations. Studies with recombinant and synthetic toxin variants on hippocampal neurons and cells expressing common receptor compositions suggest that MmTX1 and MmTX2 allosterically increase GABA A receptor susceptibility to agonist, thereby potentiating receptor opening as well as desensitization, possibly by interacting with the α + /β − interface. Moreover, hippocampal neuron excitability measurements reveal toxin-induced transitory network inhibition, followed by an increase in spontaneous activity. In concert, toxin injections into mouse brain result in reduced basal activity between intense seizures. Altogether, we characterized two animal toxins that enhance GABA A receptor sensitivity to agonist, thereby establishing a previously unidentified class of tools to study this receptor family.

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Section: Resultsmentioning

confidence: 99%

MmTX1 and MmTX2 from coral snake venom potently modulate GABA _A receptor activity

Rosso

Schwarz

Diaz-Bustamante

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Neurotoxin I from Naja mossambica mossambica contains a total of 16 methyl groups. These originate from Val-48, Ile-52, two leucines and eight threonines [29]. Most of these methyl resonances are well rcsolved in the 'H NMR spectrum at 360 MHz (Fig.…”

Section: Aromatic Protonsmentioning

confidence: 85%

“…In newer batches of the venom of Naja mossamb ica mossam b ica, this fir st small toxic peak has disappeared and the neurotoxin used in this paper now emerges first from the last chromatography. It seems therefore more appropriate to call this toxin neurotoxin I, similarly to Gregoire and Rochat [29] who have established the sequence of the molecule.…”

Section: Methodsmentioning

confidence: 99%

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The ¹H Nuclear‐Magnetic‐Resonance Spectra of Neurotoxin I and Cardiotoxin V^II4 from Naja mossambica mossambica

Lauterwein¹,

Lazdunski

Wüthrich³

1978

European Journal of Biochemistry

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Two toxins from the venom of Naju mossambicu mossambica, neurotoxin I and cardiotoxin V"4, were investigated in aqueous solution by high-resolution 'H nuclear magnetic resonance (NMR) techniques at 360 MHz. The spectral characterization of the proteins included determination of the number of slowly exchanging amide protons which can be observed in 'H20 solution, measurement of the amide proton chemical shifts and exchange rates, characterization of the aromatic spin systems and the internal mobilities of aromatic rings, and studies of the pH dependence of the NMR spectra. For numerous resonances of labile and non-labile protons quite outstanding pH titration shifts were observed. It is suggested that these NMR parameters provide a useful basis for comparative structural studies of different proteins in the large group of homologous snake toxins. As a first application the NMR data presently available in the literature on neurotoxin I1 from Naju nuja oxiuna, toxin CI from Nuja nigricollis and erabutoxin a and b from Laticaudu semfusciatu have been used to compare these three proteins with neurotoxin I from Nuja mossambica mossambicu. This preliminary comparative study provides evidence that the same type of spatial structure prevails for these four homologous neurotoxins and that the folding of the backbone corresponds quite closely to that observed in the crystal structure of erabutoxin b. A second application is the comparison of cardiotoxin V"4 from Nuju mossumbica mossambicu with the neurotoxins. The experimental data indicate that the folding of the polypeptide backbone is closely similar, but that the cardiotoxin molecule is markedly more flexible than the neurotoxins.The short neurotoxins and the cardiotoxins are a group of homologous proteins found in snake venoms. They consist typically of one polypeptide chain with 60 -62 amino acid residues, including four disulfide bridges [l, 21. The eight half-cystine residues in cardiotoxins and neurotoxins are placed at the same positions, and in addition seven other amino acid residues are found to be common to both groups of toxins. In spite of these homologies there are pronounced differences in the mode of action of the two types of toxins. Neurotoxin binds to a protein receptor at the postsynaptic level and blocks acetylcholine transmission [3]. Cardiotoxin apparently binds to a lipid-type receptor structure, and irreversibly depolarizes a wide spectrum of cells [4--81. Much effort was recently devoted to the investigation of relations between the spatial structures of Note. Neurotoxin I was previously denoted neurotoxin 11; for Abbreviatiofis. NMR, nuclear magnetic resonance; 6, chemical details see Materials and Methods. shift; ppm, parts per million. short toxins and their biological functions. These studies include theoretical predictions of the molecular conformations from the amino acid sequence [9-111, studies of chemically modified toxins [12,13], optical spectroscopy [14 -181, nuclear magnetic resonance (NMR) spectroscopy [19-221 and X-ray crys...

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“…Pelamis toxin b interestingly has glutamic acid residue at position 10. The only other toxin containing glutamic acid residue at this position is toxin I of Naja mossambica mossambica venom (Gregoire & Rochat 1977). Compared with Pelamis toxin a, toxin b differs only at position 10.…”

Section: Discussionmentioning

confidence: 99%

Isolation and Characterization of Pelamis platurus (Yellow-bellied Sea Snake) Postsynaptic Isoneurotoxin

Mori

Ishizaki

1989

Journal of Pharmacy and Pharmacology

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Pelamis platurus (yellow-bellied sea snake) venom contains several neurotoxins, the major toxin, which is most toxic, and two other isotoxins. The second most toxic neurotoxin (Pelamis toxin b) was isolated and characterized. It contains 60 amino acid residues with only one residue difference from the major toxin, Pelamis toxin a. The difference is at the tenth amino acid residue from the acid terminal. The isoelectric point of toxin b is 8.7. Raman spectroscopic examination of toxin b indicates that the toxin contains a considerable amount of antiparallel beta-structure, beta-turn, and random coil without alpha-helix as the amide I band appears at 1673 cm-1 and the amide III band at 1246 cm-1. Circular dichroic studies also indicate a typical beta-sheet structure. The Pelamis toxin b is a typical postsynaptic neurotoxin as it binds to the acetylcholine receptor competitively with a well known toxin, alpha-bungarotoxin. The LD50 of toxin b is 0.185 microgram g-1 in mice by intravenous injection, indicating high toxicity of a postsynaptic neurotoxin.

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Amino Acid Sequences of Neurotoxins I and III of the Elapidae Snake Naja mossambica mossambica

Cited by 28 publications

References 25 publications

MmTX1 and MmTX2 from coral snake venom potently modulate GABA _A receptor activity

MmTX1 and MmTX2 from coral snake venom potently modulate GABA _A receptor activity

The ¹H Nuclear‐Magnetic‐Resonance Spectra of Neurotoxin I and Cardiotoxin V^II4 from Naja mossambica mossambica

Isolation and Characterization of Pelamis platurus (Yellow-bellied Sea Snake) Postsynaptic Isoneurotoxin

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Amino Acid Sequences of Neurotoxins I and III of the Elapidae Snake Naja mossambica mossambica

Cited by 28 publications

References 25 publications

MmTX1 and MmTX2 from coral snake venom potently modulate GABA A receptor activity

MmTX1 and MmTX2 from coral snake venom potently modulate GABA A receptor activity

The 1H Nuclear‐Magnetic‐Resonance Spectra of Neurotoxin I and Cardiotoxin VII4 from Naja mossambica mossambica

Isolation and Characterization of Pelamis platurus (Yellow-bellied Sea Snake) Postsynaptic Isoneurotoxin

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MmTX1 and MmTX2 from coral snake venom potently modulate GABA _A receptor activity

MmTX1 and MmTX2 from coral snake venom potently modulate GABA _A receptor activity

The ¹H Nuclear‐Magnetic‐Resonance Spectra of Neurotoxin I and Cardiotoxin V^II4 from Naja mossambica mossambica