8SQN

CryoEM structure of Western equine encephalitis virus VLP in complex with the chimeric Du-D1-Mo-D2 MXRA8 receptor

Summary for 8SQN

• Entry DOI: 10.2210/pdb8sqn/pdb
• EMDB information: 40711
• Descriptor: DuD1MoD2 chimeric MXRA8, E1 envelope glycoprotein, E2 envelope glycoprotein, ... (4 entities in total)
• Functional Keywords: weev, mxra8, receptor, alphavirus, avian, vlp, structural genomics, psi-2, protein structure initiative, center for structural genomics of infectious diseases, csgid, viral protein-signaling protein complex, viral protein/signaling protein
• Biological source: Anas platyrhynchos (mallard); More
• Total number of polymer chains: 9
• Total formula weight: 405970.78

Authors

Zimmerman, M.I.,Fremont, D.H.,Center for Structural Genomics of Infectious Diseases (CSGID),Center for Structural Biology of Infectious Diseases (CSBID) (deposition date: 2023-05-04, release date: 2023-12-20, Last modification date: 2024-11-13)

Primary citation

Zimmerman, O.,Zimmerman, M.I.,Raju, S.,Nelson, C.A.,Errico, J.M.,Madden, E.A.,Holmes, A.C.,Hassan, A.O.,VanBlargan, L.A.,Kim, A.S.,Adams, L.J.,Basore, K.,Whitener, B.M.,Palakurty, S.,Davis-Adams, H.G.,Sun, C.,Gilliland Jr., T.,Earnest, J.T.,Ma, H.,Ebel, G.D.,Zmasek, C.,Scheuermann, R.H.,Klimstra, W.B.,Fremont, D.H.,Diamond, M.S.
Vertebrate-class-specific binding modes of the alphavirus receptor MXRA8.
Cell, 186:4818-4833.e25, 2023

PubMed Abstract: MXRA8 is a receptor for chikungunya (CHIKV) and other arthritogenic alphaviruses with mammalian hosts. However, mammalian MXRA8 does not bind to alphaviruses that infect humans and have avian reservoirs. Here, we show that avian, but not mammalian, MXRA8 can act as a receptor for Sindbis, western equine encephalitis (WEEV), and related alphaviruses with avian reservoirs. Structural analysis of duck MXRA8 complexed with WEEV reveals an inverted binding mode compared with mammalian MXRA8 bound to CHIKV. Whereas both domains of mammalian MXRA8 bind CHIKV E1 and E2, only domain 1 of avian MXRA8 engages WEEV E1, and no appreciable contacts are made with WEEV E2. Using these results, we generated a chimeric avian-mammalian MXRA8 decoy-receptor that neutralizes infection of multiple alphaviruses from distinct antigenic groups in vitro and in vivo. Thus, different alphaviruses can bind MXRA8 encoded by different vertebrate classes with distinct engagement modes, which enables development of broad-spectrum inhibitors.

PubMed: 37804831
DOI: 10.1016/j.cell.2023.09.007

Experimental method

ELECTRON MICROSCOPY (3.89 Å)