Journal: Nat Commun / Year: 2023 Title: Structural convergence endows nuclear transport receptor Kap114p with a transcriptional repressor function toward TATA-binding protein. Authors: Chung-Chi Liao / Yi-Sen Wang / Wen-Chieh Pi / Chun-Hsiung Wang / Yi-Min Wu / Wei-Yi Chen / Kuo-Chiang Hsia / 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 ...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 (yTBP). Remarkably, Kap114p wraps around the yTBP 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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