Molecular architecture and conservation of an immature human endogenous retrovirus

DOI: 10.1038/s41467-023-40786-w

Authors: Anna-Sophia Krebs (Wellcome Trust Centre for Human Genetics, University of Oxford) , Hsuan-Fu Liu (Duke University School of Medicine) , Ye Zhou (Duke University) , Juan S. Rey (University of Delaware) , Lev Levintov (University of Delaware) , Juan Shen (Wellcome Trust Centre for Human Genetics, University of Oxford) , Andrew Howe (Diamond Light Source) , Juan R. Perilla (University of Delaware) , Alberto Bartesaghi (Duke University) , Peijun Zhang (Wellcome Trust Centre for Human Genetics, University of Oxford; Diamond Light Source; Chinese Academy of Medical Sciences Oxford Institute, University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 14

State: Published (Approved)
Published: August 2023
Diamond Proposal Number(s): 21004 , 21005

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.

Diamond Keywords: Viruses; Human Endogenous Retroviruses (HERVs)

Subject Areas: Biology and Bio-materials

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: Krios III-Titan Krios III at Diamond

Added On: 27/08/2023 20:54

Documents:
s41467-023-40786-w.pdf

Discipline Tags:

Pathogens Health & Wellbeing Structural biology Life Sciences & Biotech

Technical Tags:

Microscopy Electron Microscopy (EM) Cryo Electron Microscopy (Cryo EM)