The three-dimensional structure of the toxic peptide Cl13 from the scorpion Centruroides limpidus
Por:
Estefania Lopez-Giraldo, Andrea, Olamendi-Portugal, Timoteo, Riano-Umbarila, Lidia, BECERRIL, BALTAZAR, Possani, Lourival D., Delepierre, Muriel, del Rio-Portilla, Federico
Publicada:
1 sep 2020
Categoría:
Toxicology
Resumen:
Cl13 is a toxin purified previously from the venom of the Mexican
scorpion Centruroides limpidus. This toxin affects the function of
voltage gated Na+-channels, human subtypes Nav1.4, Nav1.5 and Nav1.6 in
a similar manner as other known beta-toxins from scorpion venoms. Here,
we report a correction of the primary structure of Cl13, previously
published. The peptide does contain 66 amino acids, but residue 58 is a
tryptophan and the last C-terminal amino acid is an amidated lysine,
instead of arginine. The main contribution of this communication is the
determination of the 3D-structure of Cl13, by solution NMR, showing that
Cl13 has the classical cysteinest-abilized alpha/beta (CS alpha/beta)
folding. It has a triple stranded antiparallel beta sheet commonly
present in scorpion sodium channel beta-toxins. In addition, we report
and discuss a comparison of Cl13 structure with two other toxins (Cn2
and Css2) from scorpions of the same genus Centruroides, which shows
important surface similarities with the structure reported here.
Finally, the lack of neutralization of Cl13 toxin by two single-chain
antibody fragments (scFvs), named LR and 10FG2, which are capable of
neutralizing various toxins from Mexican scorpions, is revised. In
particular, 10FG2 is capable of neutralizing toxins Cll1 and Cll2 of the
same scorpion C. limpidus. The reasons why LR and 10FG2 are unable of
neutralizing Cl13 toxin are discussed.
Filiaciones:
Estefania Lopez-Giraldo, Andrea:
Univ Nacl Autonoma Mexico, Inst Quim, Circuito Exterior S-N,Ciudad Univ, Cdmx 04510, Mexico
Olamendi-Portugal, Timoteo:
Univ Nacl Autonoma Mexico, Inst Biotecnol, Av Univ 2001, Cuernavaca 62210, Morelos, Mexico
Riano-Umbarila, Lidia:
Univ Nacl Autonoma Mexico, Inst Biotecnol, Av Univ 2001, Cuernavaca 62210, Morelos, Mexico
Univ Nacl Autonoma Mexico, Inst Biotecnol, Catedra CONACYT, Av Univ 2001, Cuernavaca 62210, Morelos, Mexico
BECERRIL, BALTAZAR:
Univ Nacl Autonoma Mexico, Inst Biotecnol, Av Univ 2001, Cuernavaca 62210, Morelos, Mexico
Possani, Lourival D.:
Univ Nacl Autonoma Mexico, Inst Biotecnol, Av Univ 2001, Cuernavaca 62210, Morelos, Mexico
Delepierre, Muriel:
Inst Pasteur, Dept Struct Biol & Chem, UMR3528, CNRS, Paris, France
del Rio-Portilla, Federico:
Univ Nacl Autonoma Mexico, Inst Quim, Circuito Exterior S-N,Ciudad Univ, Cdmx 04510, Mexico
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