4v1d
From Proteopedia
Ternary complex among two human derived single chain antibody fragments and Cn2 toxin from scorpion Centruroides noxius.
Structural highlights
FunctionSCX2_CENNO Mammal beta-toxins bind voltage-independently at site-4 of sodium channels and shift the activation voltage to more negative potentials. This toxin is active against mammals. Publication Abstract from PubMedNowadays, the trends in the research devoted to develop novel antidotes against scorpion stings have showed excellent results with the use of recombinant antibody fragments. The polyclonal character of commercial anti-venoms, obtained through the immunization of animals and which contain several neutralizing antibodies that recognize different epitopes on the toxins, guarantees the neutralization of the venoms. To avoid the use of animals we aimed to develop an equivalent recombinant anti-venom composed of a few neutralizing single chain antibody fragments (scFvs) that bind to two different epitopes on the scorpion toxins. In this study, we obtained scFv RU1 derived from scFv C1. RU1 showed a good capacity to neutralize the Cn2 toxin and whole venom of the scorpionCentruroides noxius. Previously, we had produced scFv LR, obtained from a different parental fragment (scFv 3F). LR also showed a similar neutralizing capacity. The simultaneous administration of both scFvs resulted in improved protection, which was translated as a rapid recovery of previously envenomed animals. The crystallographic structure of the ternary complex (scFv LR-Cn2-scFv RU1) allowed us to identify the areas of interaction of both scFvs with the toxin, which correspond to non-overlapping sites. The epitope recognized by scFv RU1 seems to be related to a greater efficiency in the neutralization of the whole venom. In addition, the structural analysis of the complex helped us to explain the cross-reactivity of these scFvs and how they neutralize the venom. Optimal neutralization of Centruroides noxius venom is understood through a structural complex between two antibody fragments and the Cn2 toxin.,Riano-Umbarila L, Ledezma-Candanoza LM, Serrano-Posada H, Fernandez-Taboada G, Olamendi-Portugal T, Rojas-Trejo S, Gomez-Ramirez IV, Rudino-Pinera E, Possani LD, Becerril B J Biol Chem. 2015 Nov 20. pii: jbc.M115.685297. PMID:26589800[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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