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
ISSN: 18793150
Editorial
PERGAMON-ELSEVIER SCIENCE LTD, THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND, Reino Unido
Tipo de documento: Article
Volumen: 184 Número:
Páginas: 158-166
WOS Id: 000556890000022
ID de PubMed: 32569846