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Structure paper

TitleStructural and functional basis of VLDLR usage by Eastern equine encephalitis virus.
Journal, issue, pagesCell, Vol. 187, Issue 2, Page 360-374.e19, Year 2024
Publish dateJan 18, 2024
AuthorsLucas J Adams / Saravanan Raju / Hongming Ma / Theron Gilliland / Douglas S Reed / William B Klimstra / Daved H Fremont / Michael S Diamond /
PubMed AbstractThe 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 ...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.
External linksCell / PubMed:38176410 / PubMed Central
MethodsEM (single particle)
Resolution2.86 - 6.03 Å
Structure data

EMDB-42187: Eastern equine encephalitis virus (PE-6) VLP (icosahedral)
Method: EM (single particle) / Resolution: 3.78 Å

42188

8ufa

EMDB-42188, PDB-8ufa:
Eastern equine encephalitis virus (PE-6) VLP (asymmetric unit)
Method: EM (single particle) / Resolution: 2.86 Å

EMDB-42189: Eastern equine encephalitis virus (PE-6) VLP in complex with full-length VLDLR (icosahedral)
Method: EM (single particle) / Resolution: 4.75 Å

42190

8ufb

EMDB-42190, PDB-8ufb:
Eastern equine encephalitis virus (PE-6) VLP in complex with full-length VLDLR (asymmetric unit)
Method: EM (single particle) / Resolution: 3.89 Å

EMDB-42191: Eastern equine encephalitis virus (PE-6) VLP in complex with VLDLR LA(1-2) (icosahedral)
Method: EM (single particle) / Resolution: 4.09 Å

42192

8ufc

EMDB-42192, PDB-8ufc:
Eastern equine encephalitis virus (PE-6) VLP in complex with VLDLR LA(1-2) (asymmetric unit)
Method: EM (single particle) / Resolution: 3.09 Å

EMDB-42193: Eastern equine encephalitis virus (PE-6) VLP in complex with VLDLR LA(1-3) (icosahedral)
Method: EM (single particle) / Resolution: 4.21 Å

EMDB-42194: Eastern equine encephalitis virus (PE-6) VLP in complex with VLDLR LA(1-3) (asymmetric unit)
Method: EM (single particle) / Resolution: 3.24 Å

EMDB-42195: Eastern equine encephalitis virus (PE-6) VLP in complex with VLDLR LA(1-5)[W132A] (icosahedral)
Method: EM (single particle) / Resolution: 4.94 Å

EMDB-42196: Eastern equine encephalitis virus (PE-6) VLP in complex with VLDLR LA(1-5)[W132A] (asymmetric unit)
Method: EM (single particle) / Resolution: 3.71 Å

EMDB-42197: Eastern equine encephalitis virus (PE-6) VLP in complex with VLDLR LA(1-6)[W132A, W210A] (icosahedral)
Method: EM (single particle) / Resolution: 4.05 Å

EMDB-42198: Eastern equine encephalitis virus (PE-6) VLP in complex with VLDLR LA(1-6)[W132A, W210A] (asymmetric unit)
Method: EM (single particle) / Resolution: 2.98 Å

EMDB-42199: Eastern equine encephalitis virus (PE-6) VLP in complex with VLDLR LA(1-8)[W132A, W210A, W256A] (icosahedral)
Method: EM (single particle) / Resolution: 6.03 Å

EMDB-42200: Eastern equine encephalitis virus (PE-6) VLP in complex with VLDLR LA(1-8)[W132A, W210A, W256A] (asymmetric unit)
Method: EM (single particle) / Resolution: 4.75 Å

EMDB-42201: Eastern equine encephalitis virus (PE-6) VLP in complex with VLDLR LA(3-8) (icosahedral)
Method: EM (single particle) / Resolution: 3.66 Å

EMDB-42202: Eastern equine encephalitis virus (PE-6) VLP in complex with VLDLR LA(1-6)[W89A] (icosahedral)
Method: EM (single particle) / Resolution: 5.72 Å

EMDB-42203: Eastern equine encephalitis virus (PE-6) VLP in complex with VLDLR LA(1-6)[W89A] (asymmetric unit)
Method: EM (single particle) / Resolution: 4.26 Å

EMDB-42212: Eastern equine encephalitis virus (FL93-939) VLP in complex with VLDLR LA(1-6) (icosahedral)
Method: EM (single particle) / Resolution: 4.72 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-CA:
Unknown entry

Source
  • eastern equine encephalitis virus
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / virus / Structural Genomics / Center for Structural Biology of Infectious Diseases / CSBID / receptor

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