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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.

2024-10-02 biochemistry
10.1101/2024.10.01.616120 bioRxiv
Show 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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