8C9M

HERV-K Gag immature lattice

8C9M の概要

• エントリーDOI: 10.2210/pdb8c9m/pdb
• EMDBエントリー: 16511
• 分子名称: Gag protein (1 entity in total)
• 機能のキーワード: c6 symmetry, endogenous retrovirus, virus like particle
• 由来する生物種: Human endogenous retrovirus K
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 444415.31

構造登録者

Krebs, A.-S.,Liu, H.-F.,Zhou, Y.,Rey, J.S.,Levintov, L.,Perilla, J.R.,Bartesaghi, A.,Zhang, P. (登録日: 2023-01-23, 公開日: 2023-02-01, 最終更新日: 2024-07-24)

主引用文献

Krebs, A.S.,Liu, H.F.,Zhou, Y.,Rey, J.S.,Levintov, L.,Shen, J.,Howe, A.,Perilla, J.R.,Bartesaghi, A.,Zhang, P.
Molecular architecture and conservation of an immature human endogenous retrovirus.
Biorxiv, 2023

PubMed Abstract: A significant part of the human genome consists of endogenous retroviruses sequences. Human endogenous retrovirus K (HERV-K) is the most recently acquired endogenous retrovirus, is activated and expressed in many cancers and amyotrophic lateral sclerosis and possibly contributes to the aging process. To understand the molecular architecture of endogenous retroviruses, we determined the structure of immature HERV-K from native virus-like particles (VLPs) using cryo-electron tomography and subtomogram averaging (cryoET STA). The HERV-K VLPs show a greater distance between the viral membrane and immature capsid lattice, correlating with the presence of additional peptides, SP1 and p15, between the capsid (CA) and matrix (MA) proteins compared to the other retroviruses. The resulting cryoET STA map of the immature HERV-K capsid at 3.2 Å resolution shows a hexamer unit oligomerized through a 6-helix bundle which is further stabilized by a small molecule in the same way as the IP6 in immature HIV-1 capsid. The HERV-K immature CA hexamer assembles into the immature lattice via highly conserved dimmer and trimer interfaces, whose interactions were further detailed through all-atom molecular dynamics simulations and supported by mutational studies. A large conformational change mediated by the flexible linker between the N-terminal and the C-terminal domains of CA occurs between the immature and the mature HERV-K capsid protein, analogous to HIV-1. Comparison between HERV-K and other retroviral immature capsid structures reveals a highly conserved mechanism for the assembly and maturation of retroviruses across genera and evolutionary time.

PubMed: 37333227
DOI: 10.1101/2023.06.07.544027

実験手法

ELECTRON MICROSCOPY (3.2 Å)