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Structural basis of VCP-VCPIP1-p47 ternary complex in Golgi maintenance

Author

Listed:
  • Binita Shah

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • Moritz Hunkeler

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • Ariana Bratt

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • Hong Yue

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • Isabella Jaen Maisonet

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • Eric S. Fischer

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • Sara J. Buhrlage

    (Dana-Farber Cancer Institute
    Harvard Medical School)

Abstract

VCP/p97 regulates a wide range of cellular processes, including post-mitotic Golgi reassembly. In this context, VCP is assisted by p47, an adapter protein, and VCPIP1, a deubiquitylase (DUB). However, how they organize into a functional ternary complex to promote Golgi assembly remains unknown. Here, we use cryo-EM to characterize both VCP-VCPIP1 and VCP-VCPIP1-p47 complexes. We show that VCPIP1 engages VCP through two interfaces: one involving the N-domain of VCP and the UBX domain of VCPIP1, and the other involving the VCP D2 domains and a region of VCPIP1 we refer to as VCPID. The p47 UBX domain competitively binds to the VCP N-domain, while not affecting VCPID binding. We show that VCPID is critical for VCP-mediated enhancement of DUB activity and proper Golgi assembly. The ternary structure along with biochemical and cellular data provides new insights into the complex interplay of VCP with its co-factors.

Suggested Citation

  • Binita Shah & Moritz Hunkeler & Ariana Bratt & Hong Yue & Isabella Jaen Maisonet & Eric S. Fischer & Sara J. Buhrlage, 2025. "Structural basis of VCP-VCPIP1-p47 ternary complex in Golgi maintenance," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63161-3
    DOI: 10.1038/s41467-025-63161-3
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