6NK6

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

Summary for 6NK6

• Entry DOI: 10.2210/pdb6nk6/pdb
• Related: 6NK3
• EMDB information: 9393 9394 9395
• Descriptor: Matrix remodeling-associated protein 8, E1 glycoprotein, E2 glycoprotein, ... (5 entities in total)
• Functional Keywords: chikungunya, virus-like particle, viral receptor, mxra8, structural genomics, center for structural genomics of infectious diseases, csgid, virus like particle-signaling protein complex, virus like particle/signaling protein
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 16
• Total formula weight: 568587.24

Authors

Basore, K.,Kim, A.S.,Nelson, C.A.,Fremont, D.H.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2019-01-04, release date: 2019-05-22, Last modification date: 2024-11-20)

Primary citation

Basore, K.,Kim, A.S.,Nelson, C.A.,Zhang, R.,Smith, B.K.,Uranga, C.,Vang, L.,Cheng, M.,Gross, M.L.,Smith, J.,Diamond, M.S.,Fremont, D.H.
Cryo-EM Structure of Chikungunya Virus in Complex with the Mxra8 Receptor.
Cell, 177:1725-, 2019

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 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.

PubMed: 31080061
DOI: 10.1016/j.cell.2019.04.006

Experimental method

ELECTRON MICROSCOPY (4.06 Å)