6T61

A model of the EIAV CA-SP hexamer (C2) from Gag-deltaMA tubes assembled at pH8

6T61 の概要

• エントリーDOI: 10.2210/pdb6t61/pdb
• EMDBエントリー: 10381 10382 10383 10384 10385
• 分子名称: Gag polyprotein (1 entity in total)
• 機能のキーワード: retrovirus, lentivirus, equine infectious anemia virus, eiav, gag, capsid, ip6, phytic acid, inositolhexakiphosphate, viral protein
• 由来する生物種: Equine infectious anemia virus (EIAV)
• タンパク質・核酸の鎖数: 18
• 化学式量合計: 987867.63

構造登録者

Dick, R.A.,Xu, C.,Morado, D.R.,Kravchuk, V.,Ricana, C.L.,Lyddon, T.D.,Broad, A.M.,Feathers, J.R.,Johnson, M.C.,Vogt, V.M.,Perilla, J.R.,Briggs, J.A.G.,Schur, F.K.M. (登録日: 2019-10-17, 公開日: 2020-01-15, 最終更新日: 2024-10-16)

主引用文献

Dick, R.A.,Xu, C.,Morado, D.R.,Kravchuk, V.,Ricana, C.L.,Lyddon, T.D.,Broad, A.M.,Feathers, J.R.,Johnson, M.C.,Vogt, V.M.,Perilla, J.R.,Briggs, J.A.G.,Schur, F.K.M.
Structures of immature EIAV Gag lattices reveal a conserved role for IP6 in lentivirus assembly.
Plos Pathog., 16:e1008277-e1008277, 2020

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 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.

PubMed: 31986188
DOI: 10.1371/journal.ppat.1008277

実験手法

ELECTRON MICROSCOPY (3.7 Å)