9VFU

Structure of mature CVA6 virus complexed with 1F4 Fab

Summary for 9VFU

• Entry DOI: 10.2210/pdb9vfu/pdb
• EMDB information: 65038
• Descriptor: Genome polyprotein, VH, VL, ... (7 entities in total)
• Functional Keywords: coxsackievirus a6, krm1, receptor, virus
• Biological source: Mus musculus; More
• Total number of polymer chains: 6
• Total formula weight: 120163.33

Authors

Ke, X.,Li, X.,Liu, Z.,Liu, K.,Yan, X.,Shu, B.,Zhang, C. (deposition date: 2025-06-11, release date: 2025-11-19, Last modification date: 2026-06-10)

Primary citation

Ke, X.,Li, X.,Liu, Z.,Liu, K.,Liu, W.,Yan, X.,Shu, B.,Zhang, C.
Molecular mechanisms of receptor recognition and antibody neutralization of coxsackievirus A6.
Nat Commun, 17:934-934, 2025

PubMed Abstract: Coxsackievirus A6 (CVA6), a major cause of hand, foot, and mouth disease, lacks approved vaccines or drugs. KRM1 is its only known receptor, but its precise role remains unclear. This study investigates CVA6's entry mechanism and antibody neutralization. Cryo-EM shows CVA6 clinical strain HeB primarily exists as mature virions. KRM1 binding within the canyon triggers conversion to uncoating intermediate, defining KRM1 as an uncoating receptor for CVA6. However, KRM1 knockout reduces CVA6 infectivity without affecting attachment. Conversely, disrupting heparan sulfate proteoglycan (HSPG) impairs both viral attachment and infectivity, and CVA6 virions bind heparin directly. These results support a two-receptor entry model for CVA6: HSPG mediates viral attachment, while KRM1 induces uncoating. Additionally, we develop two CVA6-specific protective antibodies (1F4 and 3H7), targeting a new antigenic site near the three-fold axis of the viral capsid. These antibodies sterically block KRM1 binding and function post-attachment, consistent with KRM1's role. The findings elucidate CVA6 entry and offer a basis for antibody interventions.

PubMed: 41413343
DOI: 10.1038/s41467-025-67666-9

Experimental method

ELECTRON MICROSCOPY (2.11 Å)