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

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,...

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Main Authors: Chung-Chi Liao, Yi-Sen Wang, Wen-Chieh Pi, Chun-Hsiung Wang, Yi-Min Wu, Wei-Yi Chen, Kuo-Chiang Hsia
Format: Article
Language:English
Published: Nature Portfolio 2023-09-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-41206-9
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author Chung-Chi Liao
Yi-Sen Wang
Wen-Chieh Pi
Chun-Hsiung Wang
Yi-Min Wu
Wei-Yi Chen
Kuo-Chiang Hsia
author_facet Chung-Chi Liao
Yi-Sen Wang
Wen-Chieh Pi
Chun-Hsiung Wang
Yi-Min Wu
Wei-Yi Chen
Kuo-Chiang Hsia
author_sort Chung-Chi Liao
collection DOAJ
description 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.
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spelling doaj.art-c2895cd2145845c2aee349dfe692c0332023-11-20T10:05:18ZengNature PortfolioNature Communications2041-17232023-09-0114111610.1038/s41467-023-41206-9Structural convergence endows nuclear transport receptor Kap114p with a transcriptional repressor function toward TATA-binding proteinChung-Chi Liao0Yi-Sen Wang1Wen-Chieh Pi2Chun-Hsiung Wang3Yi-Min Wu4Wei-Yi Chen5Kuo-Chiang Hsia6Molecular and Cell Biology, Taiwan International Graduate Program, Academia Sinica and National Defense Medical CenterInstitute of Molecular Biology, Academia SinicaInstitute of Biochemistry and Molecular Biology, College of Life Sciences, National Yang Ming Chiao Tung UniversityInstitute of Biological Chemistry, Academia SinicaInstitute of Biological Chemistry, Academia SinicaInstitute of Biochemistry and Molecular Biology, College of Life Sciences, National Yang Ming Chiao Tung UniversityMolecular and Cell Biology, Taiwan International Graduate Program, Academia Sinica and National Defense Medical CenterAbstract 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.https://doi.org/10.1038/s41467-023-41206-9
spellingShingle Chung-Chi Liao
Yi-Sen Wang
Wen-Chieh Pi
Chun-Hsiung Wang
Yi-Min Wu
Wei-Yi Chen
Kuo-Chiang Hsia
Structural convergence endows nuclear transport receptor Kap114p with a transcriptional repressor function toward TATA-binding protein
Nature Communications
title Structural convergence endows nuclear transport receptor Kap114p with a transcriptional repressor function toward TATA-binding protein
title_full Structural convergence endows nuclear transport receptor Kap114p with a transcriptional repressor function toward TATA-binding protein
title_fullStr Structural convergence endows nuclear transport receptor Kap114p with a transcriptional repressor function toward TATA-binding protein
title_full_unstemmed Structural convergence endows nuclear transport receptor Kap114p with a transcriptional repressor function toward TATA-binding protein
title_short Structural convergence endows nuclear transport receptor Kap114p with a transcriptional repressor function toward TATA-binding protein
title_sort structural convergence endows nuclear transport receptor kap114p with a transcriptional repressor function toward tata binding protein
url https://doi.org/10.1038/s41467-023-41206-9
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