CgNa, a type I toxin from the giant Caribbean sea anemoneCondylactis giganteashows structural similarities to both type I and II toxins, as well as distinctive structural and functional properties

Abstract

CgNa (Condylactis gigantea neurotoxin) is a 47-amino-acid- residue toxin from the giant Caribbean sea anemone Condylactis gigantea. The structure of CgNa, which was solved by 1H-NMR spectroscopy, is somewhat atypical and displays significant homology with both type I and II anemone toxins. CgNa also displays a considerable number of exceptions to the canonical structural elements that are thought to be essential for the activity of this group of toxins. Furthermore, unique residues in CgNa define a characteristic structure with strong negatively charged surface patches. These patches disrupt a surface-exposed cluster of hydrophobic residues present in all anemone-derived toxins described to date. A thorough characterization by patch-clamp analysis using rat DRG (dorsal root ganglion) neurons indicated that CgNa preferentially binds to TTX-S (tetrodotoxin-sensitive) voltage-gated sodium channels in the resting state. This association increased the inactivation time constant and the rate of recovery from inactivation, inducing a significant shift in the steady state of inactivation curve to the left. The specific structural features of CgNa may explain its weaker inhibitory capacity when compared with the other type I and II anemone toxins.

Intron Retention as a Posttranscriptional Regulatory Mechanism of Neurotoxin Expression at Early Life Stages of the Starlet Anemone Nematostella vectensis

“…The disulfide bridges are in yellow. CgNa (right) is a Type I toxin (Protein Data Bank code 2h9x), 11 and ShI (left) is a Type II toxin (Protein Data Bank code 1shi). 12 The Nv1 model (middle) was constructed using SWISS-MODEL 13 according to the CgNa and ShI NMR-based structures.…”

Sea anemone toxins affecting voltage-gated sodium channels – molecular and evolutionary features

“…it seems that this “binary”classification largely focused on sequence differences between the toxins of just the first two sea anemone families investigated. The NMR structure of all Type I and Type II sea anemone toxins exhibits an anti-parallel β-sheet composed of four β-strands and a highly flexible loop, named ‘Arg-14 loop’, after its most conserved residue (Widmer et al, 1989; Fogh et al, 1990; Wilcox et al, 1993; Pallaghy et al, 1995; Monks et al, 1995; Salceda et al, 2007). …”

Structural features of cysteine-rich polypeptides from sea anemone venoms

“…Usually, the spatial structures of these toxins are very similar and comprise a nucleus including twisted four strand antiparallel β sheet connected via three loops [38][39][40][41][42]. The clearly pro nounced type I β turns (Ap A, SHNA) are also determined in a number of structures [38,42].…”

“…The clearly pro nounced type I β turns (Ap A, SHNA) are also determined in a number of structures [38,42]. The nucleus is stabilized by three disulfide bonds, part of which undergoes cis trans isomerization in the solu tion thus enhancing conformational freedom of the proteins [38][39][40][41][42]. Phylogenetic tree of the multiple sequence alignment of mature polypeptides.…”