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Structural convergence endows nuclear transport receptor Kap114p with a transcriptional repressor function toward TATA-binding protein

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  • Chung-Chi Liao

    (Academia Sinica and National Defense Medical Center
    Academia Sinica)

  • Yi-Sen Wang

    (Academia Sinica)

  • Wen-Chieh Pi

    (National Yang Ming Chiao Tung University)

  • Chun-Hsiung Wang

    (Academia Sinica)

  • Yi-Min Wu

    (Academia Sinica)

  • Wei-Yi Chen

    (National Yang Ming Chiao Tung University
    National Yang Ming Chiao Tung University)

  • Kuo-Chiang Hsia

    (Academia Sinica and National Defense Medical Center
    Academia Sinica
    National Yang Ming Chiao Tung University)

Abstract

The transcription factor TATA-box binding protein (TBP) modulates gene expression in nuclei. This process requires the involvement of nuclear transport receptors, collectively termed karyopherin-β (Kap-β) in yeast, and various regulatory factors. In previous studies we showed that Kap114p, a Kap-β that mediates nuclear import of yeast TBP (yTBP), modulates yTBP-dependent transcription. However, how Kap114p associates with yTBP to exert its multifaceted functions has remained elusive. Here, we employ single-particle cryo-electron microscopy to determine the structure of Kap114p in complex with the core domain of yTBP (yTBPC). Remarkably, Kap114p wraps around the yTBPC N-terminal lobe, revealing a structure resembling transcriptional regulators in complex with TBP, suggesting convergent evolution of the two protein groups for a common function. We further demonstrate that Kap114p sequesters yTBP away from promoters, preventing a collapse of yTBP dynamics required for yeast responses to environmental stress. Hence, we demonstrate that nuclear transport receptors represent critical elements of the transcriptional regulatory network.

Suggested Citation

  • Chung-Chi Liao & Yi-Sen Wang & Wen-Chieh Pi & Chun-Hsiung Wang & Yi-Min Wu & Wei-Yi Chen & Kuo-Chiang Hsia, 2023. "Structural convergence endows nuclear transport receptor Kap114p with a transcriptional repressor function toward TATA-binding protein," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41206-9
    DOI: 10.1038/s41467-023-41206-9
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    References listed on IDEAS

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    1. Chih-Chia Chang & Ching-Jou Chen & Cédric Grauffel & Yu-Chung Pien & Carmay Lim & Su-Yi Tsai & Kuo-Chiang Hsia, 2019. "Ran pathway-independent regulation of mitotic Golgi disassembly by Importin-α," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    2. Petra Wollmann & Sheng Cui & Ramya Viswanathan & Otto Berninghausen & Melissa N. Wells & Manuela Moldt & Gregor Witte & Agata Butryn & Petra Wendler & Roland Beckmann & David T. Auble & Karl-Peter Hop, 2011. "Structure and mechanism of the Swi2/Snf2 remodeller Mot1 in complex with its substrate TBP," Nature, Nature, vol. 475(7356), pages 403-407, July.
    3. Won-Ki Huh & James V. Falvo & Luke C. Gerke & Adam S. Carroll & Russell W. Howson & Jonathan S. Weissman & Erin K. O'Shea, 2003. "Global analysis of protein localization in budding yeast," Nature, Nature, vol. 425(6959), pages 686-691, October.
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