9W34
CryoEM structure of EV-D68 strain Fermon procapsid
Summary for 9W34
| Entry DOI | 10.2210/pdb9w34/pdb |
| EMDB information | 65590 |
| Descriptor | Capsid protein VP2, P1, Capsid protein VP1 (3 entities in total) |
| Functional Keywords | ev-d68, procapsid, viral protein |
| Biological source | enterovirus D68 More |
| Total number of polymer chains | 3 |
| Total formula weight | 87592.28 |
| Authors | Liang, S.J.,Lou, Z.Y. (deposition date: 2025-07-29, release date: 2026-08-05, Last modification date: 2026-09-09) |
| Primary citation | Liang, S.,Guo, H.,Xu, Z.,Liu, Z.,Yang, W.,Liu, X.,Wei, Z.,Hou, J.,Huang, W.,Wang, W.,Li, J.,Ma, W.,Deng, Z.,Qian, H.,Wang, Y.,Liu, J.,Rao, Z.,Wei, W.,Lou, Z. A dual-receptor checkpoint primes enterovirus D68 for respiratory cell entry. Nat Commun, 17:-, 2026 Cited by PubMed Abstract: MFSD6 is a newly identified receptor that mediates the invasion of respiratory cells by enterovirus D68 (EV-D68), a non-polio enterovirus that causes severe respiratory disease and poliomyelitis-like illness in children. Here, we report near-atomic-resolution cryo-electron microscopy (cryo-EM) structures of historical and contemporary AFM-associated EV-D68 strains, together with their complexes bound to the third extracellular loop of MFSD6 (MFSD6-L3). These structures uncover a previously unrecognized "binary gating switch" mechanism of virus-receptor engagement that differs from the reported model. In this mechanism, the N200-V208 segment of MFSD6, carrying a glycosylated Asn207, inserts into one capsomer, whereas the sialyl-Gal-terminated glycan of MFSD6 engages an adjacent capsomer. Neu5Ac binding induces conformational rearrangements that expel the pocket factor, destabilize the virion, and prime infection. Functional analyses further define the contributions of the receptor-contacting residues and glycans to viral attachment and entry. Together, our findings refine the molecular basis of EV-D68 recognition of MFSD6 and reveal a glycan-mediated dual-lock mechanism that may enhance receptor specificity, prevent premature uncoating, and ensure productive infection only upon engagement of the correct host receptor. These results provide broader insight into enterovirus tropism and establish a framework for structure-guided antiviral design. PubMed: 42637770DOI: 10.1038/s41467-026-75856-2 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.21 Å) |
Structure validation
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