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Cited by 13Cellular transport and secretionFungal and yeast genetics researchAutophagy in Disease and Therapy

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

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Chen, Kai-En, Tillu, Vikas A., Gopaldass, Navin, Chowdhury, Sudeshna Roy, Leneva, Natalya, Kovtun, Oleksiy, Ruan, Juanfang, Guo, Qian, Ariotti, Nicholas, Mayer, Andreas, Collins, Brett M.·2025·Nature Communications
DOI 10.1038/s41467-025-58846-8PMC PMC12000511

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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.

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Metadata

Authors
Chen, K.-E., Tillu, V. A., Gopaldass, N., Chowdhury, S. R., Leneva, N., Kovtun, O., Ruan, J., Guo, Q., Ariotti, N., Mayer, A., & Collins, B. M.
Affiliations
  • The University of Queensland (AU)
  • University of Lausanne (CH)
  • Max Planck Institute for Multidisciplinary Sciences (DE)
  • UNSW Sydney (AU)
Corresponding author
Collins, Brett M.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2025-04-15
Volume
16
Issue
1
Pages
3568-3568
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-025-58846-8
PMC
PMC12000511
OpenAlex
W4409444078
Cited by
13
References
10
Citations by year
2026: 8 · 2025: 5
FWCI
6.44
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • SERVAL (Université de Lausanne) (publishedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • IRIS (submittedVersion, cc-by)
  • IRIS (submittedVersion)
  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
  • MPG.PuRe (Max Planck Society) (submittedVersion, cc-by)
  • SERVAL (Université de Lausanne) (submittedVersion)
Funders
Department of Health | National Health and Medical Research Council (APP2016410)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Keywords
retromer, sorting nexins, VPS29, VPS35, Vps26, protein-protein interaction, protein complex formation, Saccharomyces cerevisiae
MeSH terms
Protein Binding, Endosomes, Saccharomyces cerevisiae, Cryoelectron Microscopy, Saccharomyces cerevisiae Proteins, Vesicular Transport Proteins, Protein Multimerization, Sorting Nexins

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