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bioRxiv · 10.1101/2024.10.01.616120

Ternary complex formation of VCP, VCPIP1 and p47 facilitates Golgi reassembly

Shah, B.·Hunkeler, M.·Bratt, A.·Yue, H.·Jaen Maisonet, I.·Fischer, E. S.·Buhrlage, S. J.
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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 deubiquitinase (DUB). However, how they organize into a functionally competent complex and promote reassembly remains unknown. Here, we use cryo-EM to characterize 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 Golgi reassembly.

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Shah, B., Hunkeler, M., Bratt, A., Yue, H., Jaen Maisonet, I., Fischer, E. S., Buhrlage, S. J.. 2024-10-02. Ternary complex formation of VCP, VCPIP1 and p47 facilitates Golgi reassembly. https://doi.org/10.1101/2024.10.01.616120

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