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*, Kuo Chiang Hsia*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number5518
JournalNature Communications
Volume14
Issue number1
DOIs
StatePublished - Dec 2023

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