We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Molecular architecture and conservation of an immature human endogenous retrovirus.
- Authors
Krebs, Anna-Sophia; Liu, Hsuan-Fu; Zhou, Ye; Rey, Juan S.; Levintov, Lev; Shen, Juan; Howe, Andrew; Perilla, Juan R.; Bartesaghi, Alberto; Zhang, Peijun
- Abstract
The human endogenous retrovirus K (HERV-K) is the most recently acquired endogenous retrovirus in the human genome and is activated and expressed in many cancers and amyotrophic lateral sclerosis. We present the immature HERV-K capsid structure at 3.2 Å resolution determined from native virus-like particles using cryo-electron tomography and subtomogram averaging. The structure shows a hexamer unit oligomerized through a 6-helix bundle, which is stabilized by a small molecule analogous to IP6 in immature HIV-1 capsid. The HERV-K immature lattice is assembled via highly conserved dimer and trimer interfaces, as detailed through all-atom molecular dynamics simulations and supported by mutational studies. A large conformational change mediated by the linker between the N-terminal and the C-terminal domains of CA occurs during HERV-K maturation. 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. The hexagonal immature capsid lattice of human endogenous retrovirus K is determined at 3.2 Å resolution, which is an assembly of small molecule-stabilized hexamers via dimer and trimer interfaces, a highly conserved mechanism among retroviruses.
- Subjects
RETROVIRUSES; AMYOTROPHIC lateral sclerosis; VIRUS-like particles; MOLECULAR dynamics; HUMAN genome; SMALL molecules
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-40786-w