IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-63161-3.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-63161-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-63161-3?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
    ---><---

    References listed on IDEAS

    as
    1. Josh Abramson & Jonas Adler & Jack Dunger & Richard Evans & Tim Green & Alexander Pritzel & Olaf Ronneberger & Lindsay Willmore & Andrew J. Ballard & Joshua Bambrick & Sebastian W. Bodenstein & David , 2024. "Addendum: Accurate structure prediction of biomolecular interactions with AlphaFold 3," Nature, Nature, vol. 636(8042), pages 4-4, December.
    2. Hisao Kondo & Catherine Rabouille & Richard Newman & Timothy P. Levine & Darryl Pappin & Paul Freemont & Graham Warren, 1997. "p47 is a cofactor for p97-mediated membrane fusion," Nature, Nature, vol. 388(6637), pages 75-78, July.
    3. Yihong Ye & Hemmo H. Meyer & Tom A. Rapoport, 2001. "The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosol," Nature, Nature, vol. 414(6864), pages 652-656, December.
    4. Kristijan Ramadan & Roland Bruderer & Fabio M. Spiga & Oliver Popp & Tina Baur & Monica Gotta & Hemmo H. Meyer, 2007. "Cdc48/p97 promotes reformation of the nucleus by extracting the kinase Aurora B from chromatin," Nature, Nature, vol. 450(7173), pages 1258-1262, December.
    5. Yang Xu & Han Han & Ian Cooney & Yuxuan Guo & Noah G. Moran & Nathan R. Zuniga & John C. Price & Christopher P. Hill & Peter S. Shen, 2022. "Active conformation of the p97-p47 unfoldase complex," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    6. Josh Abramson & Jonas Adler & Jack Dunger & Richard Evans & Tim Green & Alexander Pritzel & Olaf Ronneberger & Lindsay Willmore & Andrew J. Ballard & Joshua Bambrick & Sebastian W. Bodenstein & David , 2024. "Accurate structure prediction of biomolecular interactions with AlphaFold 3," Nature, Nature, vol. 630(8016), pages 493-500, June.
    7. Wai Cheung Chan & Xiaoxi Liu & Robert S. Magin & Nicholas M. Girardi & Scott B. Ficarro & Wanyi Hu & Maria I. Tarazona Guzman & Cara A. Starnbach & Alejandra Felix & Guillaume Adelmant & Anthony C. Va, 2023. "Accelerating inhibitor discovery for deubiquitinating enzymes," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Pantelis Livanos & Choy Kriechbaum & Sophia Remers & Arvid Herrmann & Sabine Müller, 2025. "Kinesin-12 POK2 polarization is a prerequisite for a fully functional division site and aids cell plate positioning," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    2. Justin Riper & Arleth O. Martinez-Claros & Lie Wang & Hannah E. Schneiderman & Sweta Maheshwari & Monica C. Pillon, 2025. "CryoEM structure of the SLFN14 endoribonuclease reveals insight into RNA binding and cleavage," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    3. Xin Yong & Guowen Jia & Qin Yang & Chunzhuang Zhou & Sitao Zhang & Huaqing Deng & Daniel D. Billadeau & Zhaoming Su & Da Jia, 2025. "Cryo-EM structure of the BLOC-3 complex provides insights into the pathogenesis of Hermansky-Pudlak syndrome," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    4. Camille N. Lambert & Vaitea Opuu & Francesco Calvanese & Polina Pavlinova & Francesco Zamponi & Eric J. Hayden & Martin Weigt & Matteo Smerlak & Philippe Nghe, 2025. "Exploring the space of self-reproducing ribozymes using generative models," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    5. Sara Basse Hansen & Sergio G. Bartual & Huijie Yuan & Olawale G. Raimi & Andrii Gorelik & Andrew T. Ferenbach & Kristian Lytje & Jan Skov Pedersen & Taner Drace & Thomas Boesen & Daan M. F. Aalten, 2025. "Multi-domain O-GlcNAcase structures reveal allosteric regulatory mechanisms," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    6. Chongbing Liao & Qihui Liu & Gan Luo & Yinyue Luo & Dan Yao & Qingxia Wang & Jue Zhang & Yang Wu & Jialin Jin & Dan Xu & Wuyuan Lu, 2025. "Human neutrophil α-defensin HNP1 interacts with bacterial OmpA to promote Acinetobacter baumannii biofilm formation," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    7. Jianping Kong & Wanqian Wu & Shiyue Ke & Zihan Zhou & Shenglan Xia & Jianyu Chen & Runyu Zhu & Yijia Hou & Tinashe Makanyire & Xiangru Shan & Zhuyue Zhuo & Keying Li & Hongtao Shen & Pan Yang & Pingpi, 2025. "Molecular mechanisms of CBASS phospholipase effector CapV mediated membrane disruption," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    8. Julian O. Streit & Sammy H. S. Chan & Saifu Daya & John Christodoulou, 2025. "Rational design of 19F NMR labelling sites to probe protein structure and interactions," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    9. FNU Vidya & Youran Luo & Hongwei Wu & Wilfred A. Donk & Andrew C. McShan & Vinayak Agarwal, 2025. "Large protein-like leader peptides engage differently with RiPP halogenases and lanthionine synthetases," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    10. Shuyi Zeng & Xingyu Xiong & Houfang Long & Qianhui Xu & Yifan Yu & Bo Sun & Cong Liu & Zhizhi Wang & Wenqing Xu & Shengnan Zhang & Dan Li, 2025. "Design of Ig-like binders targeting α-synuclein fibril for mitigating its pathological activities," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    11. Yu Zhang & Tingting Zhang & Xue Xiao & Yejun Wang & Adam Kawalek & Jinzhao Ou & Anmin Ren & Wenhao Sun & Vincent Bakker & Yujie Liu & Yuelong Li & Liang Yang & Liang Ye & Ning Jia & Jan-Willem Veening, 2025. "CRISPRi screen identifies FprB as a synergistic target for gallium therapy in Pseudomonas aeruginosa," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    12. Dhana G. Gorasia & Eric Hanssen & Manasi Mudaliyar & Craig J. Morton & Sepideh Valimehr & Christine Seers & Lianyi Zhang & Matthew T. Doyle & Debnath Ghosal & Paul D. Veith & Eric C. Reynolds, 2025. "Insights into type IX secretion from PorKN cogwheel structure bound to PorG and attachment complexes," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    13. Xiaorong Li & Xiaoxu Yang & Xiaoli Lu & Bingqian Lin & Yuanyuan Zhang & Bangdong Huang & Yutong Zhou & Jing Huang & Kun Wu & Qiang Zhou & Ximin Chi, 2025. "Structural basis for substrate recognition mechanism of human SLC26A7," Nature Communications, Nature, vol. 16(1), pages 1-10, December.
    14. Ai Tamura & Kazuyuki Yamagata & Takashi Kono & Masanori Fujimoto & Takahiro Fuchigami & Motoi Nishimura & Masataka Yokoyama & Akitoshi Nakayama & Naoko Hashimoto & Ikki Sakuma & Nobuyuki Mitsukawa & Y, 2025. "p53-inducible lncRNA LOC644656 causes genotoxic stress-induced stem cell maldifferentiation and cancer chemoresistance," Nature Communications, Nature, vol. 16(1), pages 1-22, December.
    15. Gašper Šolinc & Marija Srnko & Franci Merzel & Ana Crnković & Mirijam Kozorog & Marjetka Podobnik & Gregor Anderluh, 2025. "Cryo-EM structures of a protein pore reveal a cluster of cholesterol molecules and diverse roles of membrane lipids," Nature Communications, Nature, vol. 16(1), pages 1-11, December.
    16. Minghua Hou & Yuhao Xia & Pengcheng Wang & Zexin lv & Dongliang Hou & Xiaogen Zhou & Jianyang Zeng & Guijun Zhang, 2025. "High-accuracy protein complex structure modeling based on sequence-derived structure complementarity," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    17. Tae-Kyeong Jeong & R. Ciaran MacKenzie Frater & Jongha Yoon & Anja Groth & Ji-Joon Song, 2025. "CODANIN-1 sequesters ASF1 by using a histone H3 mimic helix to regulate the histone supply," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    18. Mike Sleutel & Ravi R. Sonani & Jessalyn G. Miller & Fengbin Wang & Andres Gonzalez Socorro & Yang Chen & Reece Martin & Borries Demeler & Michael J. Rudolph & Vikram Alva & Han Remaut & Edward H. Ege, 2025. "Donor strand complementation and calcium ion coordination drive the chaperone-free polymerization of archaeal cannulae," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    19. Carmen Ebenwaldner & Antonio Ginés García Saura & Simon Ekström & Katja Bernfur & Martin Moche & Derek T. Logan & Michael S. Cohen & Herwig Schüler, 2025. "Regulation of ADP-ribosyltransferase activity by ART domain dimerization in PARP15," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    20. Tianyu Liu & Tinglin Huang & Lijun Wang & Yingxin Lin & Rex Ying & Hongyu Zhao, 2025. "UNICORN: Towards universal cellular expression prediction with a multi-task learning framework," Nature Communications, Nature, vol. 16(1), pages 1-14, December.

    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_s41467-025-63161-3. 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.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.