|Title||Cryo-EM Structure of Chikungunya Virus in Complex with the Mxra8 Receptor.|
|Journal, issue, pages||Cell, Vol. 177, Issue 7, Page 1725-1737.e16, Year 2019|
|Publish date||Jun 13, 2019|
|Authors||Katherine 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 Abstract||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 ...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 links||PubMed:31080061 / Publisher's page|
|Keywords||CELL 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|
|Methods||EM (single particle, icos. sym.) / X-ray diffraction / EM (single particle)|
|Resolution||2.2 - 4.99 A|
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