7X2I
Cryo-EM structure of Coxsackievirus B1 pre-A particle in complex with nAb 2E6 (CVB1-pre-A:2E6)
Summary for 7X2I
| Entry DOI | 10.2210/pdb7x2i/pdb |
| EMDB information | 32968 |
| Descriptor | 2E6 light chain, 2E6 heavy chain, Virion protein 1, ... (6 entities in total) |
| Functional Keywords | coxsackievirus b1, neutralizing antiboy, cryo-em, virus |
| Biological source | Mus musculus More |
| Total number of polymer chains | 6 |
| Total formula weight | 118954.46 |
| Authors | |
| Primary citation | Zheng, Q.,Zhu, R.,Yin, Z.,Xu, L.,Sun, H.,Yu, H.,Wu, Y.,Jiang, Y.,Huang, Q.,Huang, Y.,Zhang, D.,Liu, L.,Yang, H.,He, M.,Zhou, Z.,Jiang, Y.,Chen, Z.,Zhao, H.,Que, Y.,Kong, Z.,Zhou, L.,Li, T.,Zhang, J.,Luo, W.,Gu, Y.,Cheng, T.,Li, S.,Xia, N. Structural basis for the synergistic neutralization of coxsackievirus B1 by a triple-antibody cocktail. Cell Host Microbe, 30:1279-, 2022 Cited by PubMed Abstract: Coxsackievirus B1 (CVB1) is an emerging pathogen associated with severe neonatal diseases including aseptic meningitis, myocarditis, and pancreatitis and also with the development of type 1 diabetes. We characterize the binding and therapeutic efficacies of three CVB1-specific neutralizing antibodies (nAbs) identified for their ability to inhibit host receptor engagement. High-resolution cryo-EM structures showed that these antibodies recognize different epitopes but with an overlapping region in the capsid VP2 protein and specifically the highly variable EF loop. Moreover, they perturb capsid-receptor interactions by binding various viral particle forms. Antibody combinations achieve synergetic neutralization via a stepwise capsid transition and virion disruption, indicating dynamic changes in the virion in response to multiple nAbs targeting the receptor-binding site. Furthermore, this three-antibody cocktail protects against lethal challenge in neonatal mice and limits pancreatitis and viral replication in a non-obese diabetic mouse model. These results illustrate the utility of nAbs for rational design of therapeutics against picornaviruses such as CVB. PubMed: 36002016DOI: 10.1016/j.chom.2022.08.001 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.29 Å) |
Structure validation
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