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Structural and functional basis of VLDLR usage by Eastern equine encephalitis virus.
Adams, Lucas J; Raju, Saravanan; Ma, Hongming; Gilliland, Theron; Reed, Douglas S; Klimstra, William B; Fremont, Daved H; Diamond, Michael S.
Afiliación
  • Adams LJ; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Raju S; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Ma H; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Gilliland T; The Center for Vaccine Research and Department of Immunology, The University of Pittsburgh, Pittsburgh, PA 15261, USA.
  • Reed DS; The Center for Vaccine Research and Department of Immunology, The University of Pittsburgh, Pittsburgh, PA 15261, USA.
  • Klimstra WB; The Center for Vaccine Research and Department of Immunology, The University of Pittsburgh, Pittsburgh, PA 15261, USA.
  • Fremont DH; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Biochemistry & Molecular Biophysics, Washington University School
  • Diamond MS; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 6311
Cell ; 187(2): 360-374.e19, 2024 01 18.
Article en En | MEDLINE | ID: mdl-38176410
ABSTRACT
The very-low-density lipoprotein receptor (VLDLR) comprises eight LDLR type A (LA) domains and supports entry of distantly related alphaviruses, including Eastern equine encephalitis virus (EEEV) and Semliki Forest virus (SFV). Here, by resolving multiple cryo-electron microscopy structures of EEEV-VLDLR complexes and performing mutagenesis and functional studies, we show that EEEV uses multiple sites (E1/E2 cleft and E2 A domain) to engage more than one LA domain simultaneously. However, no single LA domain is necessary or sufficient to support efficient EEEV infection. Whereas all EEEV strains show conservation of two VLDLR-binding sites, the EEEV PE-6 strain and a few other EEE complex members feature a single amino acid substitution that enables binding of LA domains to an additional site on the E2 B domain. These structural and functional analyses informed the design of a minimal VLDLR decoy receptor that neutralizes EEEV infection and protects mice from lethal challenge.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Receptores de LDL / Microscopía por Crioelectrón / Virus de la Encefalitis Equina del Este / Encefalomielitis Equina Límite: Animals Idioma: En Revista: Cell Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Receptores de LDL / Microscopía por Crioelectrón / Virus de la Encefalitis Equina del Este / Encefalomielitis Equina Límite: Animals Idioma: En Revista: Cell Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos