IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-58894-0.html
   My bibliography  Save this article

Cryo-EM structure of the AAA+ SPATA5 complex and its role in human cytoplasmic pre-60S maturation

Author

Listed:
  • Yuhao Dai

    (Peking University
    Peking University)

  • Damu Wu

    (Peking University
    Peking University)

  • Ningning Li

    (Peking University)

  • Chengying Ma

    (Peking University)

  • Yunyang Zhang

    (Peking University)

  • Ning Gao

    (Peking University
    Peking University
    Peking University)

Abstract

Eukaryotic ribosome biogenesis is an energy-consuming process involving many ATPase-driven steps. In yeast, AAA+ protein Drg1 releases an assembly factor Rlp24, a placeholder for Rpl24, from pre-60S particles just exported to cytosol. The equivalent process in human cells involves SPATA5 (Drg1 homolog) and additional factors. However, the mechanistic details remain unclear. Here we reveal that SPATA5 forms a 4:2:2:2 complex with SPATA5L1, C1orf109, and CINP. This complex features an N-terminal ring made of C1orf109, CINP and NTDs of SPATA5/SPATA5L1, and two hexameric AAA+ ATPase rings. Intriguingly, a conserved cysteine C672 in the P-loop of SPATA5 is sulfinylated, generating an inactive conformation incompatible with ATP binding. We also obtained a cryo-EM structure of pre-60S-bound SPATA5 complex. Different from yeast, the recognition of the pre-60S particle is mediated by human-specific factor CINP, through two distinct sets of interactions: one with GTPBP4 and the other with ES27A. Taken together, these data provide structural basis for understanding the cytoplasmic maturation of the pre-60S, and reveal human-specific features that might be harnessed for therapeutic purposes.

Suggested Citation

  • Yuhao Dai & Damu Wu & Ningning Li & Chengying Ma & Yunyang Zhang & Ning Gao, 2025. "Cryo-EM structure of the AAA+ SPATA5 complex and its role in human cytoplasmic pre-60S maturation," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58894-0
    DOI: 10.1038/s41467-025-58894-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-58894-0
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-025-58894-0?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
    ---><---

    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:16:y:2025:i:1:d:10.1038_s41467-025-58894-0. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.