Cryo-EM Structure of Chikungunya Virus in Complex with the Mxra8 Receptor.
Cell
; 177(7): 1725-1737.e16, 2019 06 13.
Article
en En
| MEDLINE
| ID: mdl-31080061
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 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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Virus Chikungunya
/
Proteínas del Envoltorio Viral
/
Proteínas de la Membrana
Límite:
Humans
Idioma:
En
Año:
2019
Tipo del documento:
Article