4V1D

Ternary complex among two human derived single chain antibody fragments and Cn2 toxin from scorpion Centruroides noxius.

Summary for 4V1D

• Entry DOI: 10.2210/pdb4v1d/pdb
• Descriptor: SINGLE CHAIN ANTIBODY FRAGMENT LR, HEAVY CHAIN, SINGLE CHAIN ANTIBODY FRAGMENT LR, LIGHT CHAIN, BETA-MAMMAL TOXIN CN2, ... (6 entities in total)
• Functional Keywords: toxin-immune system complex, human scfv, scorpion venom neutralization, directed evolution, cn2 toxin., toxin/immune system
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Secreted: 4V1D
• Total number of polymer chains: 5
• Total formula weight: 64315.96

Authors

Riano-Umbarila, L.,Serrano-Posada, H.,Rojas-Trejo, S.,Rudino-Pinera, E.,Becerril, B. (deposition date: 2014-09-25, release date: 2015-10-07, Last modification date: 2024-11-13)

Primary citation

Riano-Umbarila, L.,Ledezma-Candanoza, L.M.,Serrano-Posada, H.,Fernandez-Taboada, G.,Olamendi-Portugal, T.,Rojas-Trejo, S.,Gomez-Ramirez, I.V.,Rudino-Pinera, E.,Possani, L.D.,Becerril, B.
Optimal Neutralization of Centruroides Noxius Venom is Understood Through a Structural Complex between Two Antibody Fragments and the Cn2 Toxin.
J.Biol.Chem., 291:1619-, 2016

PubMed Abstract: The current trend of using recombinant antibody fragments in research to develop novel antidotes against scorpion stings has achieved excellent results. The polyclonal character of commercial antivenoms, 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 antivenom 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 scorpion Centruroides 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 poisoned 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.

PubMed: 26589800
DOI: 10.1074/JBC.M115.685297

Experimental method

X-RAY DIFFRACTION (3.1 Å)