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,...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Nature Portfolio
2023-09-01
|
Series: | Nature Communications |
Online Access: | https://doi.org/10.1038/s41467-023-41206-9 |
_version_ | 1797558335199772672 |
---|---|
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. |
first_indexed | 2024-03-10T17:28:48Z |
format | Article |
id | doaj.art-c2895cd2145845c2aee349dfe692c033 |
institution | Directory Open Access Journal |
issn | 2041-1723 |
language | English |
last_indexed | 2024-03-10T17:28:48Z |
publishDate | 2023-09-01 |
publisher | Nature Portfolio |
record_format | Article |
series | Nature Communications |
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 |
work_keys_str_mv | AT chungchiliao structuralconvergenceendowsnucleartransportreceptorkap114pwithatranscriptionalrepressorfunctiontowardtatabindingprotein AT yisenwang structuralconvergenceendowsnucleartransportreceptorkap114pwithatranscriptionalrepressorfunctiontowardtatabindingprotein AT wenchiehpi structuralconvergenceendowsnucleartransportreceptorkap114pwithatranscriptionalrepressorfunctiontowardtatabindingprotein AT chunhsiungwang structuralconvergenceendowsnucleartransportreceptorkap114pwithatranscriptionalrepressorfunctiontowardtatabindingprotein AT yiminwu structuralconvergenceendowsnucleartransportreceptorkap114pwithatranscriptionalrepressorfunctiontowardtatabindingprotein AT weiyichen structuralconvergenceendowsnucleartransportreceptorkap114pwithatranscriptionalrepressorfunctiontowardtatabindingprotein AT kuochianghsia structuralconvergenceendowsnucleartransportreceptorkap114pwithatranscriptionalrepressorfunctiontowardtatabindingprotein |