5L21
Crystal structure of BoNT/A receptor binding domain in complex with VHH C2
Summary for 5L21
| Entry DOI | 10.2210/pdb5l21/pdb |
| Descriptor | Botulinum neurotoxin type A, VHH-C2 (3 entities in total) |
| Functional Keywords | neutralizing antibody; vhh; botulinum neurotoxin; bont-a-vhh complex, toxin |
| Biological source | Clostridium botulinum (strain Hall / ATCC 3502 / NCTC 13319 / Type A) More |
| Total number of polymer chains | 2 |
| Total formula weight | 63204.32 |
| Authors | |
| Primary citation | Yao, G.,Lam, K.H.,Weisemann, J.,Peng, L.,Krez, N.,Perry, K.,Shoemaker, C.B.,Dong, M.,Rummel, A.,Jin, R. A camelid single-domain antibody neutralizes botulinum neurotoxin A by blocking host receptor binding. Sci Rep, 7:7438-7438, 2017 Cited by PubMed Abstract: Antibody treatment is currently the only available countermeasure for botulism, a fatal illness caused by flaccid paralysis of muscles due to botulinum neurotoxin (BoNT) intoxication. Among the seven major serotypes of BoNT/A-G, BoNT/A poses the most serious threat to humans because of its high potency and long duration of action. Prior to entering neurons and blocking neurotransmitter release, BoNT/A recognizes motoneurons via a dual-receptor binding process in which it engages both the neuron surface polysialoganglioside (PSG) and synaptic vesicle glycoprotein 2 (SV2). Previously, we identified a potent neutralizing antitoxin against BoNT/A1 termed ciA-C2, derived from a camelid heavy-chain-only antibody (VHH). In this study, we demonstrate that ciA-C2 prevents BoNT/A1 intoxication by inhibiting its binding to neuronal receptor SV2. Furthermore, we determined the crystal structure of ciA-C2 in complex with the receptor-binding domain of BoNT/A1 (HA1) at 1.68 Å resolution. The structure revealed that ciA-C2 partially occupies the SV2-binding site on HA1, causing direct interference of HA1 interaction with both the N-glycan and peptide-moiety of SV2. Interestingly, this neutralization mechanism is similar to that of a monoclonal antibody in clinical trials, despite that ciA-C2 is more than 10-times smaller. Taken together, these results enlighten our understanding of BoNT/A1 interactions with its neuronal receptor, and further demonstrate that inhibiting toxin binding to the host receptor is an efficient countermeasure strategy. PubMed: 28785006DOI: 10.1038/s41598-017-07457-5 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.68 Å) |
Structure validation
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