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Structure paper

TitleCryo-EM Structure of Chikungunya Virus in Complex with the Mxra8 Receptor.
Journal, issue, pagesCell, Vol. 177, Issue 7, Page 1725-1737.e16, Year 2019
Publish dateJun 13, 2019
AuthorsKatherine Basore / Arthur S Kim / Christopher A Nelson / Rong Zhang / Brittany K Smith / Carla Uranga / Lo Vang / Ming Cheng / Michael L Gross / Jonathan Smith / Michael S Diamond / Daved H Fremont /
PubMed AbstractMxra8 is a receptor for multiple arthritogenic alphaviruses that cause debilitating acute and chronic musculoskeletal disease in humans. Herein, we present a 2.2 Å resolution X-ray crystal ...Mxra8 is a receptor for multiple arthritogenic alphaviruses that cause debilitating acute and chronic musculoskeletal disease in humans. Herein, we present a 2.2 Å resolution X-ray crystal structure of Mxra8 and 4 to 5 Å resolution cryo-electron microscopy reconstructions of Mxra8 bound to chikungunya (CHIKV) virus-like particles and infectious virus. The Mxra8 ectodomain contains two strand-swapped Ig-like domains oriented in a unique disulfide-linked head-to-head arrangement. Mxra8 binds by wedging into a cleft created by two adjacent CHIKV E2-E1 heterodimers in one trimeric spike and engaging a neighboring spike. Two binding modes are observed with the fully mature VLP, with one Mxra8 binding with unique contacts. Only the high-affinity binding mode was observed in the complex with infectious CHIKV, as viral maturation and E3 occupancy appear to influence receptor binding-site usage. Our studies provide insight into how Mxra8 binds CHIKV and creates a path for developing alphavirus entry inhibitors.
External linksPubMed:31080061 / Publisher's page
KeywordsCELL INVASION / Chikungunya / virus receptor / Immunoglobulin-like / Structural Genomics / Center for Structural Genomics of Infectious Diseases / CSGID / VIRUS LIKE PARTICLE / virus-like particle / VIRUS LIKE PARTICLE/SIGNALING PROTEIN / viral receptor / Mxra8 / VIRUS LIKE PARTICLE-SIGNALING PROTEIN complex / VIRUS
MethodsEM (single particle, icos. sym.) / X-ray diffraction / EM (single particle)
Resolution2.2 - 4.99 A
Structure data

EMDB-9393:
Electron Cryo-Microscopy Of Chikungunya VLP

EMDB-9394:
Electron Cryo-Microscopy Of Chikungunya VLP in complex with mouse Mxra8 receptor

EMDB-9395:
Electron Cryo-Microscopy of Chikungunya in Complex with Mouse Mxra8 Receptor

PDB-6nk3:
Crystal structure of murine Mxra8 ectodomain

PDB-6nk5:
Electron Cryo-Microscopy Of Chikungunya VLP

PDB-6nk6:
Electron Cryo-Microscopy Of Chikungunya VLP in complex with mouse Mxra8 receptor

PDB-6nk7:
Electron Cryo-Microscopy of Chikungunya in Complex with Mouse Mxra8 Receptor

Chemicals

ChemComp-HOH:
WATERWater

ChemComp-NAG:
N-ACETYL-D-GLUCOSAMINEN-Acetylglucosamine

Source
  • chikungunya virus
  • chikungunya virus (strain 37997)
  • mus musculus (house mouse)
  • chikungunya virus strain senegal 37997

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