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-Structure paper
タイトル | The receptor VLDLR binds Eastern Equine Encephalitis virus through multiple distinct modes. |
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ジャーナル・号・ページ | Nat Commun, Vol. 15, Issue 1, Page 6866, Year 2024 |
掲載日 | 2024年8月10日 |
著者 | Duanfang Cao / Bingting Ma / Ziyi Cao / Xiaoyu Xu / Xinzheng Zhang / Ye Xiang / |
PubMed 要旨 | Eastern Equine Encephalitis virus (EEEV) is an alphavirus that can cause severe diseases in infected humans. The very low-density lipoprotein receptor (VLDLR) was recently identified as a receptor of ...Eastern Equine Encephalitis virus (EEEV) is an alphavirus that can cause severe diseases in infected humans. The very low-density lipoprotein receptor (VLDLR) was recently identified as a receptor of EEEV. Herein, we performed cryo-electron microscopy structural and biochemistry studies on the specific interactions between EEEV and VLDLR. Our results show that VLDLR binds EEEV at three different sites A, B and C through its membrane-distal LDLR class A (LA) repeats. Site A is located in the cleft in between the E1-E2 heterodimers. Site B is located near the connecting β ribbon of E2 and is in proximity to site A, while site C is on the domain B of E2. The binding of VLDLR LAs to EEEV is in complex modes, including the LA1-2 and LA3-5 mediated two major modes. Disruption of the LA1-2 mediated binding significantly affect the cell attachment of EEEV. However, the mutation W132G of VLDLR impairs the binding of LA3, drives the switch of the binding modes, and significantly enhances the attachment of EEEV to the cell. The W132G variant of VLDLR could be identified in human genome and SNP sequences, implying that people with similar mutations in VLDLR may be highly susceptible to EEEV infection. |
リンク | Nat Commun / PubMed:39127734 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.4 - 11.0 Å |
構造データ | EMDB-38370, PDB-8xi4: EMDB-38371, PDB-8xi5: EMDB-38376: Overall structure of Eastern Equine Encephalitis VLP in complex with the receptor VLDLR LA1-2 EMDB-38377: Overall structure of Eastern Equine Encephalitis VLP in complex with the receptor VLDLR LA3-5 EMDB-38378: Structure of Eastern Equine Encephalitis VLP in complex with the receptor VLDLR LA1-8 EMDB-38379: Structure of Eastern Equine Encephalitis VLP incubated with ApoER2 isoform2 LA1-3 (no receptor binding) EMDB-38380: Structure of Eastern Equine Encephalitis VLP in complex with the receptor VLDLR LA1-3 EMDB-38381: Structure of Eastern Equine Encephalitis VLP in complex with the receptor VLDLR LA2-3 EMDB-38382: Structure of Eastern Equine Encephalitis VLP in complex with the receptor VLDLR LA1-6-W132A EMDB-38383: Structure of Eastern Equine Encephalitis VLP PE6-K156A in complex with the receptor VLDLR LA1-8 EMDB-38384: Structure of Eastern Equine Encephalitis VLP PE6-K206E in complex with the receptor VLDLR LA1-8 |
化合物 | ChemComp-CA: |
由来 |
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キーワード | VIRAL PROTEIN / East Equine Encephalitis virus / EEEV / receptor / complex / VLDLR / glycoprotein / VIRUS LIKE PARTICLE / Eastern Equine Encephalitis virus / alphavirus |