9UZP

Cryo-EM Structure of the Vaccinia Virus Entry/Fusion Complex (EFC) Including the F9 Subunit

Summary for 9UZP

• Entry DOI: 10.2210/pdb9uzp/pdb
• EMDB information: 64648
• Descriptor: Virion membrane protein OPG143, Entry-fusion complex protein OPG076, Entry-fusion complex protein OPG094, ... (10 entities in total)
• Functional Keywords: vaccinia virus, entry-fusion complex (efc), cryo-em, single-particle reconstruction, viral protein
• Biological source: Orthopoxvirus vaccinia; More
• Total number of polymer chains: 16
• Total formula weight: 288760.29

Authors

Wang, C.H.,Lin, C.S.H.,Chang, W. (deposition date: 2025-05-16, release date: 2025-12-17, Last modification date: 2026-01-28)

Primary citation

Lin, C.S.,Li, C.A.,Wang, C.H.,Kao, C.F.,Chiu, H.J.,Yeh, M.C.,Gao, H.D.,Ho, M.C.,Lee, H.M.,Chang, W.
Cryo-EM structure of the vaccinia virus entry fusion complex reveals a multicomponent fusion machinery.
Sci Adv, 12:eaec0254-eaec0254, 2026

PubMed Abstract: Membrane fusion is essential for viral entry. Unlike class I-III fusion proteins, vaccinia virus (VACV) uses a multicomponent entry fusion complex (EFC). Using cryo-electron microscopy, we determined the full-length structure of the VACV EFC at near-atomic resolution, revealing a 15-protein asymmetric assembly organized into three layers. The central A16/G9/J5 heterotrimer forms the fusion core, stabilized by conserved PXXCW and Delta motifs, and anchors two A28/H2 adaptor dimers linked to peripheral G3/L5/A21/O3 scaffolds. Structural and evolutionary analyses identify a conserved N-terminal domain in A16 containing a myristoyl-binding pocket and a phenylalanine-rich region that stabilizes the trimer and may regulate lipid engagement. An additional component, F9, binds peripherally to J5, A21, and H2 through Delta-like motifs, reinforcing the prefusion architecture. Together, these results define the VACV EFC as a unique multiprotein fusion machinery and provide a structural framework for understanding the mechanism of poxvirus entry and membrane fusion.

PubMed: 41533782
DOI: 10.1126/sciadv.aec0254

Experimental method

ELECTRON MICROSCOPY (3.05 Å)