9GCN
Co-crystal VHH (TPL1158_01_C09) - alpha-cobratoxin (Naja kaouthia)
Summary for 9GCN
| Entry DOI | 10.2210/pdb9gcn/pdb |
| Descriptor | Protein. Variable Domain of Heavy-Chain only Antibodies (VHH), Alpha-cobratoxin (3 entities in total) |
| Functional Keywords | nanobody, vhh, atibody, antitoxin, toxin, snake toxin, antivenom, neutralising, neutralizing |
| Biological source | Vicugna pacos More |
| Total number of polymer chains | 8 |
| Total formula weight | 85916.70 |
| Authors | Rivera-de-Torre, E.,Burlet, N.J.,Laustsen, A.H.,Morth, J.P. (deposition date: 2024-08-02, release date: 2025-08-06, Last modification date: 2025-08-13) |
| Primary citation | Damsbo, A.,Burlet, N.J.,Fernandez-Quintero, M.L.,Benard-Valle, M.,Overath, M.D.,Guadarrama-Martinez, A.,Vlamynck, A.,Bisbo, I.,Villalobos, C.,Tulika, T.,Alagon, A.,Loeffler, J.R.,Ward, A.B.,Boddum, K.,Morth, J.P.,Rivera-de-Torre, E.,Laustsen, A.H. Structural mechanisms behind the neutralisation of long-chain alpha-neurotoxins by broadly neutralising V H Hs discovered using a consensus antigen. Commun Chem, 8:209-209, 2025 Cited by PubMed Abstract: Snakebite envenoming, a neglected tropical disease, affects millions globally, causing significant morbidity and mortality. Developing broadly neutralising monoclonal antibodies offers a promising approach to address the antigenic variation present in snake venoms. In this study, we designed a long-chain consensus α-neurotoxin, LCC, to serve as an antigen in a phage display-based antibody discovery campaign. Utilising a yeast expression system, we expressed LCC and identified 21 variable domains of heavy-chain-only antibodies (VHs) from immune libraries. These VHs were assessed for their binding affinity to various long-chain α-neurotoxins and their neutralising capability in vitro. The VH with the broadest cross-reactivity and highest affinity, TPL1158_01_C09, was co-crystallised with α-cobratoxin to elucidate its binding mechanism. In vivo rodent studies demonstrated the neutralisation potential of TPL1158_01_C09. Our findings highlight that the use of a consensus toxin as an antigen coincided with the discovery of broadly neutralising VHs against snake venom toxins. PubMed: 40681851DOI: 10.1038/s42004-025-01600-4 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3 Å) |
Structure validation
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