IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-58846-8.html
   My bibliography  Save this article

Molecular basis for the assembly of the Vps5-Vps17 SNX-BAR proteins with Retromer

Author

Listed:
  • Kai-En Chen

    (the University of Queensland)

  • Vikas A. Tillu

    (the University of Queensland)

  • Navin Gopaldass

    (University of Lausanne)

  • Sudeshna Roy Chowdhury

    (University of Lausanne)

  • Natalya Leneva

    (Max Planck Institute for Multidisciplinary Sciences)

  • Oleksiy Kovtun

    (Max Planck Institute for Multidisciplinary Sciences)

  • Juanfang Ruan

    (University of New South Wales)

  • Qian Guo

    (the University of Queensland)

  • Nicholas Ariotti

    (the University of Queensland)

  • Andreas Mayer

    (University of Lausanne)

  • Brett M. Collins

    (the University of Queensland)

Abstract

Retromer mediates endosomal retrieval of transmembrane proteins in all eukaryotes and was first discovered in yeast in complex with the Vps5 and Vps17 sorting nexins (SNXs). Cryoelectron tomography (cryoET) studies of Retromer–Vps5 revealed a pseudo-helical coat on membrane tubules where dimers of the Vps26 subunit bind Vps5 membrane-proximal domains. However, the Vps29 subunit is also required for Vps5–Vps17 association despite being far from the membrane. Here, we show that Vps5 binds both Vps29 and Vps35 subunits through its unstructured N-terminal domain. A Pro-Leu (PL) motif in Vps5 binds Vps29 and is required for association with Retromer on membrane tubules in vitro, and for the proper recycling of the Vps10 cargo in Saccharomyces cerevisiae. CryoET of Retromer tubules with Vps5–Vps17 heterodimers show a similar architecture to the coat with Vps5–Vps5 homodimers, however, the spatial relationship between Retromer units is highly restricted, likely due to more limited orientations for docking. These results provide mechanistic insights into how Retromer and SNX-BAR association has evolved across species.

Suggested Citation

  • Kai-En Chen & Vikas A. Tillu & Navin Gopaldass & Sudeshna Roy Chowdhury & Natalya Leneva & Oleksiy Kovtun & Juanfang Ruan & Qian Guo & Nicholas Ariotti & Andreas Mayer & Brett M. Collins, 2025. "Molecular basis for the assembly of the Vps5-Vps17 SNX-BAR proteins with Retromer," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58846-8
    DOI: 10.1038/s41467-025-58846-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-58846-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-58846-8?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_s41467-025-58846-8. 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.