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

Chung-Chi Liao, Yi-Sen Wang, Wen-Chieh Pi, Chun-Hsiung Wang, Yi-Min Wu, Wei-Yi Chen () and Kuo-Chiang Hsia ()
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Chung-Chi Liao: Academia Sinica and National Defense Medical Center
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
Kuo-Chiang Hsia: Academia Sinica and National Defense Medical Center

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-41206-9

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