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-Structure paper
| タイトル | Molecular basis of ApoER2-mediated Semliki Forest virus entry. |
|---|---|
| ジャーナル・号・ページ | Nat Commun, Vol. 17, Issue 1, Page 845, Year 2025 |
| 掲載日 | 2025年12月19日 |
著者 | Bingchen Du / Xiyong Song / Bingyu Zhao / Zhibin Shi / Zaisi Liu / Shida Wang / Lili Wei / Xijun He / Juha T Huiskonen / Decheng Yang / Jingfei Wang / ![]() |
| PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:41419770 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.7 - 4.2 Å |
| 構造データ | ![]() EMDB-53901: Icosahedral reconstruction of Semliki Forest virus in complex with ApoER2 LA5 EMDB-53902, PDB-9rbq: EMDB-53903, PDB-9rbr: ![]() EMDB-53904: Composite density map of Semliki Forest virus in complex with ApoER2 LA5 ![]() EMDB-53905: Icosahedral reconstruction of Semliki Forest virus in complex with ApoER2 ligand-binding domain ![]() EMDB-53906: Semliki Forest virus trimer 1 in complex with ApoER2 ligand-binding domain ![]() EMDB-53907: Semliki Forest virus trimer 2 in complex with ApoER2 ligand-binding domain ![]() EMDB-53908: Composite density map of Semliki Forest virus in complex with ApoER2 ligand-binding domain |
| 化合物 | ![]() ChemComp-CA: |
| 由来 |
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キーワード | VIRUS / Semliki Forest virus / SFV / ApoER2 receptor / localized reconstruction |
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semliki forest virus (セムリキ森林ウイルス)
homo sapiens (ヒト)
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