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TitleStructure of Venezuelan equine encephalitis virus in complex with the LDLRAD3 receptor.
Journal, issue, pagesNature, Vol. 598, Issue 7882, Page 672-676, Year 2021
Publish dateOct 13, 2021
AuthorsKatherine Basore / Hongming Ma / Natasha M Kafai / Samantha Mackin / Arthur S Kim / Christopher A Nelson / Michael S Diamond / Daved H Fremont /
PubMed AbstractLDLRAD3 is a recently defined attachment and entry receptor for Venezuelan equine encephalitis virus (VEEV), a New World alphavirus that causes severe neurological disease in humans. Here we present ...LDLRAD3 is a recently defined attachment and entry receptor for Venezuelan equine encephalitis virus (VEEV), a New World alphavirus that causes severe neurological disease in humans. Here we present near-atomic-resolution cryo-electron microscopy reconstructions of VEEV virus-like particles alone and in a complex with the ectodomains of LDLRAD3. Domain 1 of LDLRAD3 is a low-density lipoprotein receptor type-A module that binds to VEEV by wedging into a cleft created by two adjacent E2-E1 heterodimers in one trimeric spike, and engages domains A and B of E2 and the fusion loop in E1. Atomic modelling of this interface is supported by mutagenesis and anti-VEEV antibody binding competition assays. Notably, VEEV engages LDLRAD3 in a manner that is similar to the way that arthritogenic alphaviruses bind to the structurally unrelated MXRA8 receptor, but with a much smaller interface. These studies further elucidate the structural basis of alphavirus-receptor interactions, which could inform the development of therapies to mitigate infection and disease against multiple members of this family.
External linksNature / PubMed:34646020 / PubMed Central
MethodsEM (single particle)
Resolution4.2 - 4.97 Å
Structure data

24116

7n1h

EMDB-24116, PDB-7n1h:
CryoEM structure of Venezuelan equine encephalitis virus VLP in complex with the LDLRAD3 receptor
Method: EM (single particle) / Resolution: 4.3 Å

24117

7n1i

EMDB-24117, PDB-7n1i:
CryoEM structure of Venezuelan equine encephalitis virus VLP
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-24394:
Unsharpened electron microscopy map of Venezuelan equine encephalitis VLP in complex with Domains 1 and 2 of LDLRAD3 receptor
Method: EM (single particle) / Resolution: 4.97 Å

Chemicals

ChemComp-CA:
Unknown entry

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • venezuelan equine encephalitis virus
  • mus musculus (house mouse)
KeywordsVIRUS LIKE PARTICLE / VEEV / viral envelope / host receptor / low-density lipoprotein receptor type-A module / LDLRAD3 / encephalitic alphavirus / Structural Genomics / Center for Structural Genomics of Infectious Diseases / CSGID / VLP

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