Molecular architecture and conservation of an immature human endogenous retrovirus.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
24 08 2023
Historique:
received: 14 01 2023
accepted: 09 08 2023
medline: 28 8 2023
pubmed: 25 8 2023
entrez: 24 8 2023
Statut: epublish

Résumé

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.

Identifiants

pubmed: 37620323
doi: 10.1038/s41467-023-40786-w
pii: 10.1038/s41467-023-40786-w
pmc: PMC10449913
doi:

Substances chimiques

Capsid Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

5149

Commentaires et corrections

Type : UpdateOf

Informations de copyright

© 2023. Springer Nature Limited.

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Auteurs

Anna-Sophia Krebs (AS)

Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.

Hsuan-Fu Liu (HF)

Department of Biochemistry, Duke University School of Medicine, Durham, NC, 27710, USA.

Ye Zhou (Y)

Department of Computer Science, Duke University, Durham, NC, 27708, USA.

Juan S Rey (JS)

Department of Chemistry and Biochemistry, University of Delaware, Newark, DE, 19716, USA.

Lev Levintov (L)

Department of Chemistry and Biochemistry, University of Delaware, Newark, DE, 19716, USA.

Juan Shen (J)

Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.

Andrew Howe (A)

Diamond Light Source, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK.

Juan R Perilla (JR)

Department of Chemistry and Biochemistry, University of Delaware, Newark, DE, 19716, USA. jperilla@udel.edu.

Alberto Bartesaghi (A)

Department of Biochemistry, Duke University School of Medicine, Durham, NC, 27710, USA. alberto.bartesaghi@duke.edu.
Department of Computer Science, Duke University, Durham, NC, 27708, USA. alberto.bartesaghi@duke.edu.
Department of Electrical and Computer Engineering, Duke University, Durham, NC, 27708, USA. alberto.bartesaghi@duke.edu.

Peijun Zhang (P)

Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK. peijun.zhang@strubi.ox.ac.uk.
Diamond Light Source, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK. peijun.zhang@strubi.ox.ac.uk.
Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, OX3 7BN, UK. peijun.zhang@strubi.ox.ac.uk.

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Classifications MeSH