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-Structure paper
Title | Cryogenic electron microscopy and tomography reveal imperfect icosahedral symmetry in alphaviruses. |
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Journal, issue, pages | PNAS Nexus, Vol. 3, Issue 3, Page pgae102, Year 2024 |
Publish date | Mar 7, 2024 |
Authors | David Chmielewski / Guan-Chin Su / Jason T Kaelber / Grigore D Pintilie / Muyuan Chen / Jing Jin / Albert J Auguste / Wah Chiu / |
PubMed Abstract | Alphaviruses are spherical, enveloped RNA viruses with two-layered icosahedral architecture. The structures of many alphaviruses have been studied using cryogenic electron microscopy (cryo-EM) ...Alphaviruses are spherical, enveloped RNA viruses with two-layered icosahedral architecture. The structures of many alphaviruses have been studied using cryogenic electron microscopy (cryo-EM) reconstructions, which impose icosahedral symmetry on the viral particles. Using cryogenic electron tomography (cryo-ET), we revealed a polarized symmetry defect in the icosahedral lattice of Chikungunya virus (CHIKV) in situ, similar to the late budding particles, suggesting the inherent imperfect symmetry originates from the final pinch-off of assembled virions. We further demonstrated this imperfect symmetry is also present in in vitro purified CHIKV and Mayaro virus, another arthritogenic alphavirus. We employed a subparticle-based single-particle analysis protocol to circumvent the icosahedral imperfection and boosted the resolution of the structure of the CHIKV to ∼3 Å resolution, which revealed detailed molecular interactions between glycoprotein E1-E2 heterodimers in the transmembrane region and multiple lipid-like pocket factors located in a highly conserved hydrophobic pocket. This complementary use of in situ cryo-ET and single-particle cryo-EM approaches provides a more precise structural description of near-icosahedral viruses and valuable insights to guide the development of structure-based antiviral therapies against alphaviruses. |
External links | PNAS Nexus / PubMed:38525304 / PubMed Central |
Methods | EM (single particle) / EM (subtomogram averaging) |
Resolution | 3.09 - 9.5 Å |
Structure data | EMDB-28979, PDB-8fcg: EMDB-41096: Cryo-electron tomography of Chikungunya virus pentamer structure EMDB-41631: Cryo-EM structure of Chikungunya virus with asymmetric reconstruction EMDB-41637: Asymmetric cryoEM reconstruction of Mayaro virus |
Chemicals | ChemComp-PCW: |
Source |
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Keywords | VIRUS / CHIKV asymmetric unit |