@article{1edfd86a8a774d7b9ae78d1e41a815df,
title = "Cryo-EM Structure of Chikungunya Virus in Complex with the Mxra8 Receptor",
abstract = "Basore et al. describe an X-ray crystal structure of Mxra8, an entry receptor for arthritogenic alphaviruses, and cryo-EM structures of Mxra8 bound to CHIKV. Mxra8 has an unusual Ig-like domain architecture with a head-to-head arrangement, with domain 1 emanating from a loop of domain 2. Mxra8 binds into a complex quaternary cleft formed between two E2-E1 heterodimers within a trimeric spike, while also contacting E1 from a neighboring spike. Mxra8 occupancy is lower when E3 protein is retained on the virion.",
keywords = "HDX mass spectrometry, alphavirus, cryo-electron microscopy, infection, protein crystallography, surface plasmon resonance, virus receptor",
author = "Katherine Basore and Kim, {Arthur S.} and Nelson, {Christopher A.} and Rong Zhang and Smith, {Brittany K.} and Carla Uranga and Lo Vang and Ming Cheng and Gross, {Michael L.} and Jonathan Smith and Diamond, {Michael S.} and Fremont, {Daved H.}",
note = "Funding Information: This study was supported by NIH grants R01AI114816 , R01AI123348 , R01AI095436 , and T32AI007172 and contract HHSN272201700060C ( CSGID ). The mass spectrometry was supported by NIH P41GM103422 . We thank J. Fitzpatrick, M. Rau, and M. Tobias of the Washington University Center for Cellular Imaging for assistance with cryo-EM data collection and processing; Rui Zhang of Washington University for helpful suggestions; J. Nix of ALS beamline 4.2.2 for assistance with X-ray diffraction collection and processing; and J. Alexander of PaxVax for critical comments on the manuscript. Funding Information: This study was supported by NIH grants R01AI114816, R01AI123348, R01AI095436, and T32AI007172 and contract HHSN272201700060C (CSGID). The mass spectrometry was supported by NIH P41GM103422. We thank J. Fitzpatrick, M. Rau, and M. Tobias of the Washington University Center for Cellular Imaging for assistance with cryo-EM data collection and processing; Rui Zhang of Washington University for helpful suggestions; J. Nix of ALS beamline 4.2.2 for assistance with X-ray diffraction collection and processing; and J. Alexander of PaxVax for critical comments on the manuscript. K.B. undertook the cryo-EM reconstructions and asymmetric unit atomic modeling with support from C.A.N. and D.H.F. A.S.K. engineered and purified the Mxra8 proteins and developed crystallization conditions. C.A.N. A.S.K. and D.H.F. solved the Mxra8 structure. B.S. aided in Mxra8 model building. K.B. performed and analyzed the SPR and BLI data. R.Z. performed the CHIKV infection experiments and provided key virus reagents. C.U. and L.V. produced and purified the CHIKV VLPs. J.S. provided key resources for CHIKV VLP generation. M.C. and M.L.G. performed and analyzed the HDX epitope mapping. K.B. and A.S.K. performed data analysis. M.S.D. K.B. and D.H.F. wrote the initial manuscript draft, with the other authors providing editorial comments. M.S.D. is a consultant for Inbios and Atreca and is on the Scientific Advisory Board of Moderna. D.H.F. is a founder of Courier Therapeutics. L.V. and J.S. are employees of and have equity in PaxVax, which has a vaccine program for emerging viruses, including CHIKV. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = jun,
day = "13",
doi = "10.1016/j.cell.2019.04.006",
language = "English",
volume = "177",
pages = "1725--1737.e16",
journal = "Cell",
issn = "0092-8674",
number = "7",
}