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-Structure paper
| Title | Structures of immature EIAV Gag lattices reveal a conserved role for IP6 in lentivirus assembly. |
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| Journal, issue, pages | PLoS Pathog, Vol. 16, Issue 1, Page e1008277, Year 2020 |
| Publish date | Jan 27, 2020 |
 Authors | Robert A Dick / Chaoyi Xu / Dustin R Morado / Vladyslav Kravchuk / Clifton L Ricana / Terri D Lyddon / Arianna M Broad / J Ryan Feathers / Marc C Johnson / Volker M Vogt / Juan R Perilla / John A G Briggs / Florian K M Schur /     |
| PubMed Abstract | Retrovirus assembly is driven by the multidomain structural protein Gag. Interactions between the capsid domains (CA) of Gag result in Gag multimerization, leading to an immature virus particle that ...Retrovirus assembly is driven by the multidomain structural protein Gag. Interactions between the capsid domains (CA) of Gag result in Gag multimerization, leading to an immature virus particle that is formed by a protein lattice based on dimeric, trimeric, and hexameric protein contacts. Among retroviruses the inter- and intra-hexamer contacts differ, especially in the N-terminal sub-domain of CA (CANTD). For HIV-1 the cellular molecule inositol hexakisphosphate (IP6) interacts with and stabilizes the immature hexamer, and is required for production of infectious virus particles. We have used in vitro assembly, cryo-electron tomography and subtomogram averaging, atomistic molecular dynamics simulations and mutational analyses to study the HIV-related lentivirus equine infectious anemia virus (EIAV). In particular, we sought to understand the structural conservation of the immature lentivirus lattice and the role of IP6 in EIAV assembly. Similar to HIV-1, IP6 strongly promoted in vitro assembly of EIAV Gag proteins into virus-like particles (VLPs), which took three morphologically highly distinct forms: narrow tubes, wide tubes, and spheres. Structural characterization of these VLPs to sub-4Å resolution unexpectedly showed that all three morphologies are based on an immature lattice with preserved key structural components, highlighting the structural versatility of CA to form immature assemblies. A direct comparison between EIAV and HIV revealed that both lentiviruses maintain similar immature interfaces, which are established by both conserved and non-conserved residues. In both EIAV and HIV-1, IP6 regulates immature assembly via conserved lysine residues within the CACTD and SP. Lastly, we demonstrate that IP6 stimulates in vitro assembly of immature particles of several other retroviruses in the lentivirus genus, suggesting a conserved role for IP6 in lentiviral assembly. |
 External links | PLoS Pathog / PubMed:31986188 / PubMed Central |
| Methods | EM (subtomogram averaging) / EM (tomography) |
| Resolution | 3.7 - 3.9 Å |
| Structure data | EMDB-10381: A 3.7 Angstrom structure of the EIAV CA-SP hexamer (C2) from Gag-deltaMA tubes assembled at pH8  EMDB-10382: EMDB-10383: A structure of the EIAV CA-SP hexamer (C2) from Gag-deltaMA tubes assembled at pH6 EMDB-10384: A structure of the EIAV CA-SP hexamer (C6) from Gag-deltaMA spheres assembled at pH6  EMDB-10385:  EMDB-10386: |
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 Keywords | VIRAL PROTEIN / Retrovirus / lentivirus / Equine infectious anemia virus / EIAV / Gag / capsid / IP6 / phytic acid / inositolhexakiphosphate |
equine infectious anemia virus