IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-58807-1.html
   My bibliography  Save this article

Identification of RING E3 pseudoligases in the TRIM protein family

Author

Listed:
  • Jane Dudley-Fraser

    (The Francis Crick Institute)

  • Diego Esposito

    (The Francis Crick Institute)

  • Katherine A. McPhie

    (The Francis Crick Institute)

  • Coltrane Morley-Williams

    (The Francis Crick Institute)

  • Tania Auchynnikava

    (The Francis Crick Institute)

  • Katrin Rittinger

    (The Francis Crick Institute)

Abstract

TRIpartite Motif (TRIM) family proteins have diverse roles across a broad variety of cellular functions, which are largely presumed to depend on their ubiquitin E3 ligase activity, conferred by a RING domain. However, recent reports have shown that some TRIMs lack detectable ubiquitination activity in isolation, despite containing a RING domain. Here, we present parallel in cellulo, in vitro, and in silico structure-function analyses of the ubiquitin E3 ligase activity and RING domain structural characteristics of the whole TRIM protein family. In-depth follow-up studies of this comprehensive dataset reveals a number of ‘pseudoligases’, whose RING domains have structurally diverged at either the homodimerisation or E2~ubiquitin interfaces, thereby disrupting their ability to catalyse ubiquitin transfer. Together, these data raise intriguing open questions regarding the unknown TRIM functions in physiology and disease.

Suggested Citation

  • Jane Dudley-Fraser & Diego Esposito & Katherine A. McPhie & Coltrane Morley-Williams & Tania Auchynnikava & Katrin Rittinger, 2025. "Identification of RING E3 pseudoligases in the TRIM protein family," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58807-1
    DOI: 10.1038/s41467-025-58807-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-58807-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-58807-1?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. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
    2. 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.
    3. Jiajing Chen & Zikang Wang & Xudong Guo & Fudong Li & Qingtao Wei & Xuwen Chen & Deshun Gong & Yanxin Xu & Wen Chen & Yongrui Liu & Jiuhong Kang & Yunyu Shi, 2019. "TRIM66 reads unmodified H3R2K4 and H3K56ac to respond to DNA damage in embryonic stem cells," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    4. Pengran Wang & Shirine Benhenda & Haiyan Wu & Valérie Lallemand-Breitenbach & Tao Zhen & Florence Jollivet & Laurent Peres & Yuwen Li & Sai-Juan Chen & Zhu Chen & Hugues Thé & Guoyu Meng, 2018. "Publisher Correction: RING tetramerization is required for nuclear body biogenesis and PML sumoylation," Nature Communications, Nature, vol. 9(1), pages 1-1, December.
    5. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
    6. Benjamin Stieglitz & Rohini R. Rana & Marios G. Koliopoulos & Aylin C. Morris-Davies & Veronique Schaeffer & Evangelos Christodoulou & Steven Howell & Nicholas R. Brown & Ivan Dikic & Katrin Rittinger, 2013. "Structural basis for ligase-specific conjugation of linear ubiquitin chains by HOIP," Nature, Nature, vol. 503(7476), pages 422-426, November.
    7. Diego Esposito & Jane Dudley-Fraser & Acely Garza-Garcia & Katrin Rittinger, 2022. "Divergent self-association properties of paralogous proteins TRIM2 and TRIM3 regulate their E3 ligase activity," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    8. Ying Qin & Qi Li & Wenbo Liang & Rongzhen Yan & Li Tong & Mutian Jia & Chunyuan Zhao & Wei Zhao, 2021. "TRIM28 SUMOylates and stabilizes NLRP3 to facilitate inflammasome activation," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    9. Anna Plechanovová & Ellis G. Jaffray & Michael H. Tatham & James H. Naismith & Ronald T. Hay, 2012. "Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis," Nature, Nature, vol. 489(7414), pages 115-120, September.
    10. 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.
    11. Pengran Wang & Shirine Benhenda & Haiyan Wu & Valérie Lallemand-Breitenbach & Tao Zhen & Florence Jollivet & Laurent Peres & Yuwen Li & Sai-Juan Chen & Zhu Chen & Hugues Thé & Guoyu Meng, 2018. "RING tetramerization is required for nuclear body biogenesis and PML sumoylation," Nature Communications, Nature, vol. 9(1), pages 1-10, 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. 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.
    2. William J. Nicolas & Anna Shiriaeva & Michael W. Martynowycz & Angus C. Grey & Yasmeen N. Ruma & Paul J. Donaldson & Tamir Gonen, 2025. "Structure of the lens MP20 mediated adhesive junction," Nature Communications, Nature, vol. 16(1), pages 1-10, December.
    3. 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.
    4. James Hodgkinson-Bean & Rafael Ayala & Nadishka Jayawardena & Georgia L. Rutter & Bridget N. J. Watson & David Mayo-Muñoz & James Keal & Peter C. Fineran & Matthias Wolf & Mihnea Bostina, 2025. "Global structural survey of the flagellotropic myophage φTE infecting agricultural pathogen Pectobacterium atrosepticum," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    5. Yu Wang & Sen Wang & Yuanyuan Chen & Chunlan Xie & Haibo Xu & Yunhua Lin & Ranxun Lin & Wanlin Zeng & Xuan Chen & Xinyi Nie & Shihua Wang, 2025. "The role of Npt1 in regulating antifungal protein activity in filamentous fungi," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    6. Qi Gao & Florian W. Hofer & Sebastian Filbeck & Bram J. A. Vermeulen & Martin Würtz & Annett Neuner & Charlotte Kaplan & Maja Zezlina & Cornelia Sala & Hyesu Shin & Oliver J. Gruss & Elmar Schiebel & , 2025. "Structural mechanisms for centrosomal recruitment and organization of the microtubule nucleator γ-TuRC," Nature Communications, Nature, vol. 16(1), pages 1-23, December.
    7. Tongqing Li & Steven E. Stayrook & Wenxue Li & Yueyue Wang & Hengyi Li & Jianan Zhang & Yansheng Liu & Daryl E. Klein, 2025. "Crystal structure of Isthmin-1 and reassessment of its functional role in pre-adipocyte signaling," Nature Communications, Nature, vol. 16(1), pages 1-11, December.
    8. Ruifang Ma & Bowen Du & Chen Shi & Lei Wang & Fuxing Zeng & Jie Han & Huiyi Guan & Yong Wang & Kaige Yan, 2025. "Molecular basis for the regulation of human phosphorylase kinase by phosphorylation and Ca2+," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    9. Tanmoy Paul & Chunli Yan & Jina Yu & Susan E. Tsutakawa & John A. Tainer & Dong Wang & Ivaylo Ivanov, 2025. "Molecular model of TFIIH recruitment to the transcription-coupled repair machinery," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    10. Diego Esposito & Jane Dudley-Fraser & Acely Garza-Garcia & Katrin Rittinger, 2022. "Divergent self-association properties of paralogous proteins TRIM2 and TRIM3 regulate their E3 ligase activity," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    11. Ji Huang & Liang Tong, 2025. "Molecular insights into the overall architecture of human rixosome," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    12. Z. Faidon Brotzakis & Shengyu Zhang & Mhd Hussein Murtada & Michele Vendruscolo, 2025. "AlphaFold prediction of structural ensembles of disordered proteins," Nature Communications, Nature, vol. 16(1), pages 1-9, December.
    13. Jiaxin Tan & Yuan Xiao & Fang Kong & Jiawei Qian & Angqi Zhu & Chuangye Yan, 2025. "Structural insights into thyroid hormone transporter MCT8," Nature Communications, Nature, vol. 16(1), pages 1-9, December.
    14. Haaris A. Safdari & Martino Morici & Ana Sanchez-Castro & Andrea Dallapè & Helge Paternoga & Anna Maria Giuliodori & Attilio Fabbretti & Pohl Milón & Daniel N. Wilson, 2025. "The translation inhibitors kasugamycin, edeine and GE81112 target distinct steps during 30S initiation complex formation," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    15. Florian Malard & Kristen Dias & Margaux Baudy & Stéphane Thore & Brune Vialet & Philippe Barthélémy & Sébastien Fribourg & Fedor V. Karginov & Sébastien Campagne, 2025. "Molecular basis for the calcium-dependent activation of the ribonuclease EndoU," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    16. Qianqian Ming & Daniel Antfolk & David A. Price & Anna Manturova & Elliot Medina & Srishti Singh & Charlotte Mason & Timothy H. Tran & Keiran S. M. Smalley & Daisy W. Leung & Vincent C. Luca, 2024. "Structural basis for mouse LAG3 interactions with the MHC class II molecule I-Ab," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    17. Paloma García Casas & Michela Rossini & Linnea Påvénius & Mezida Saeed & Nikita Arnst & Sonia Sonda & Tânia Fernandes & Irene D’Arsiè & Matteo Bruzzone & Valeria Berno & Andrea Raimondi & Maria Livia , 2024. "Simultaneous detection of membrane contact dynamics and associated Ca2+ signals by reversible chemogenetic reporters," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    18. Cornelia Sala & Martin Würtz & Enrico Salvatore Atorino & Annett Neuner & Patrick Partscht & Thomas Hoffmann & Sebastian Eustermann & Elmar Schiebel, 2024. "An interaction network of inner centriole proteins organised by POC1A-POC1B heterodimer crosslinks ensures centriolar integrity," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    19. Juan G. Carvajal-Patiño & Vincent Mallet & David Becerra & Luis Fernando Niño Vasquez & Carlos Oliver & Jérôme Waldispühl, 2025. "RNAmigos2: accelerated structure-based RNA virtual screening with deep graph learning," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    20. Jianan Zhang & Yuko Tsutsui & Hengyi Li & Tongqing Li & Yueyue Wang & Salma Laraki & Sofia Alarcon-Frias & Steven E. Stayrook & Daryl E. Klein, 2025. "Structural basis for the interaction between the Drosophila RTK Sevenless (dROS1) and the GPCR BOSS," Nature Communications, Nature, vol. 16(1), pages 1-12, 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_s41467-025-58807-1. 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.