9RBR

Semliki Forest virus trimer 2 in complex with ApoER2 LA5

Summary for 9RBR

• Entry DOI: 10.2210/pdb9rbr/pdb
• EMDB information: 53903
• Descriptor: Protein E3, Structural polyprotein, Envelope glycoprotein E2, ... (7 entities in total)
• Functional Keywords: semliki forest virus, sfv, apoer2 receptor, localized reconstruction, virus
• Biological source: Semliki Forest virus; More
• Total number of polymer chains: 12
• Total formula weight: 401616.90

Authors

Song, X.,Du, B.,Yang, D.,Wang, J.,Huiskonen, J.T. (deposition date: 2025-05-27, release date: 2026-01-14)

Primary citation

Du, B.,Song, X.,Zhao, B.,Shi, Z.,Liu, Z.,Wang, S.,Wei, L.,He, X.,Huiskonen, J.T.,Yang, D.,Wang, J.
Molecular basis of ApoER2-mediated Semliki Forest virus entry.
Nat Commun, 2025

PubMed Abstract: The very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) serve as entry receptors for the Semliki Forest virus (SFV). VLDLR interacts with the SFV E1 domain III (DIII) through multiple LDLR class A (LA) domains. However, the ApoER2-mediated SFV entry mechanism remains unclear. Here, we perform biochemical and cellular results and determine the cryogenic electron microscopy (cryo-EM) structures of SFV complexed with ApoER2 LA5 and full-length ApoER2, demonstrating that among the seven LA domains of ApoER2 isoform 1, only LA5 specifically binds to the SFV E1-DIII via a limited interface (353 Ų) and facilitates cell attachment and entry. Site-directed mutagenesis confirms the significance of the residues at the SFV-ApoER2 interface. Significantly, a soluble LA5 decoy receptor neutralizes SFV infection and protects mice from lethal SFV challenge. These findings reveal a LA5-dependent receptor engagement mechanism for SFV entry via ApoER2, distinct from VLDLR.

PubMed: 41419770
DOI: 10.1038/s41467-025-67550-6

Experimental method

ELECTRON MICROSCOPY (2.7 Å)