IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-40786-w.html
   My bibliography  Save this article

Molecular architecture and conservation of an immature human endogenous retrovirus

Author

Listed:
  • 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, Harwell Science and Innovation Campus)

  • Juan R. Perilla

    (University of Delaware)

  • Alberto Bartesaghi

    (Duke University School of Medicine
    Duke University
    Duke University)

  • Peijun Zhang

    (Wellcome Trust Centre for Human Genetics, University of Oxford
    Diamond Light Source, Harwell Science and Innovation Campus
    Chinese Academy of Medical Sciences Oxford Institute, University of Oxford)

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.

Suggested Citation

  • Anna-Sophia Krebs & Hsuan-Fu Liu & Ye Zhou & Juan S. Rey & Lev Levintov & Juan Shen & Andrew Howe & Juan R. Perilla & Alberto Bartesaghi & Peijun Zhang, 2023. "Molecular architecture and conservation of an immature human endogenous retrovirus," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40786-w
    DOI: 10.1038/s41467-023-40786-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-40786-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-40786-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Martin Obr & Clifton L. Ricana & Nadia Nikulin & Jon-Philip R. Feathers & Marco Klanschnig & Andreas Thader & Marc C. Johnson & Volker M. Vogt & Florian K. M. Schur & Robert A. Dick, 2021. "Structure of the mature Rous sarcoma virus lattice reveals a role for IP6 in the formation of the capsid hexamer," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    2. Robert A. Dick & Kaneil K. Zadrozny & Chaoyi Xu & Florian K. M. Schur & Terri D. Lyddon & Clifton L. Ricana & Jonathan M. Wagner & Juan R. Perilla & Barbie K. Ganser-Pornillos & Marc C. Johnson & Owen, 2018. "Inositol phosphates are assembly co-factors for HIV-1," Nature, Nature, vol. 560(7719), pages 509-512, August.
    3. Oliver Acton & Tim Grant & Giuseppe Nicastro & Neil J. Ball & David C. Goldstone & Laura E. Robertson & Kasim Sader & Andrea Nans & Andres Ramos & Jonathan P. Stoye & Ian A. Taylor & Peter B. Rosentha, 2019. "Structural basis for Fullerene geometry in a human endogenous retrovirus capsid," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    4. Robert A. Dick & Kaneil K. Zadrozny & Chaoyi Xu & Florian K. M. Schur & Terri D. Lyddon & Clifton L. Ricana & Jonathan M. Wagner & Juan R. Perilla & Barbie K. Ganser-Pornillos & Marc C. Johnson & Owen, 2018. "Author Correction: Inositol phosphates are assembly co-factors for HIV-1," Nature, Nature, vol. 563(7731), pages 22-22, November.
    5. Jiying Ning & Gonca Erdemci-Tandogan & Ernest L. Yufenyuy & Jef Wagner & Benjamin A. Himes & Gongpu Zhao & Christopher Aiken & Roya Zandi & Peijun Zhang, 2016. "In vitro protease cleavage and computer simulations reveal the HIV-1 capsid maturation pathway," Nature Communications, Nature, vol. 7(1), pages 1-12, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Anna T. Gres & Karen A. Kirby & William M. McFadden & Haijuan Du & Dandan Liu & Chaoyi Xu & Alexander J. Bryer & Juan R. Perilla & Jiong Shi & Christopher Aiken & Xiaofeng Fu & Peijun Zhang & Ashwanth, 2023. "Multidisciplinary studies with mutated HIV-1 capsid proteins reveal structural mechanisms of lattice stabilization," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Alex Kleinpeter & Donna L. Mallery & Nadine Renner & Anna Albecka & J. Ole Klarhof & Eric O. Freed & Leo C. James, 2024. "HIV-1 adapts to lost IP6 coordination through second-site mutations that restore conical capsid assembly," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Sucharita Sarkar & Kaneil K. Zadrozny & Roman Zadorozhnyi & Ryan W. Russell & Caitlin M. Quinn & Alex Kleinpeter & Sherimay Ablan & Hamed Meshkin & Juan R. Perilla & Eric O. Freed & Barbie K. Ganser-P, 2023. "Structural basis of HIV-1 maturation inhibitor binding and activity," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40786-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.