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Structure paper

TitleStructural insights into Semiliki forest virus receptor binding modes indicate novel mechanism of virus endocytosis.
Journal, issue, pagesPLoS Pathog, Vol. 20, Issue 12, Page e1012770, Year 2024
Publish dateDec 20, 2024
AuthorsDecheng Yang / Nan Wang / Bingchen Du / Zhenzhao Sun / Shida Wang / Xijun He / Jinyue Wang / Tao Zheng / Yutao Chen / Xiangxi Wang / Jingfei Wang /
PubMed AbstractThe Very Low-Density Lipoprotein Receptor (VLDLR) is an entry receptor for the prototypic alphavirus Semliki Forest Virus (SFV). However, the precise mechanisms underlying the entry of SFV into cells ...The Very Low-Density Lipoprotein Receptor (VLDLR) is an entry receptor for the prototypic alphavirus Semliki Forest Virus (SFV). However, the precise mechanisms underlying the entry of SFV into cells mediated by VLDLR remain unclear. In this study, we found that of the eight class A (LA) repeats of the VLDLR, only LA2, LA3, and LA5 specifically bind to the native SFV virion while synergistically promoting SFV cell attachment and entry. Furthermore, the multiple cryo-electron microscopy structures of VLDLR-SFV complexes and mutagenesis studies have demonstrated that under physiological conditions, VLDLR primarily binds to E1-DIII of site-1, site-2, and site-1' at the twofold symmetry axes of SFV virion through LA2, LA3, and LA5, respectively. These findings unveil a novel mechanism for viral entry mediated by receptors, suggesting that conformational transitions in VLDLR induced by multivalent binding of LAs facilitate cellular internalization of SFV, with significant implications for the design of antiviral therapeutics.
External linksPLoS Pathog / PubMed:39705215 / PubMed Central
MethodsEM (single particle)
Resolution3.02 - 3.7 Å
Structure data

39616

8yvy

EMDB-39616, PDB-8yvy:
Semliki Forest virus virion
Method: EM (single particle) / Resolution: 3.02 Å

39617

8yvz

EMDB-39617, PDB-8yvz:
Semliki Forest virus viron
Method: EM (single particle) / Resolution: 3.45 Å

39618

8yw0

EMDB-39618, PDB-8yw0:
Semliki Forest virus viron
Method: EM (single particle) / Resolution: 3.55 Å

39619

8yw1

EMDB-39619, PDB-8yw1:
Semliki Forest virus viron in complex with VLDLR
Method: EM (single particle) / Resolution: 3.44 Å

39620

8yw2

EMDB-39620, PDB-8yw2:
Semliki Forest virus viron in complex with VLDLR
Method: EM (single particle) / Resolution: 3.7 Å

Chemicals

ChemComp-CA:
Unknown entry

Source
  • semliki forest virus 4
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / Semliki Forest virus virion / VLDLR / Semliki Forest virus viron / Semliki Forest virus

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