The TFIIS N-terminal domain (TND): a transcription assembly module at the interface of order and disorder

Biochem Soc Trans. 2023 Feb 27;51(1):125-135. doi: 10.1042/BST20220342.

Abstract

Interaction scaffolds that selectively recognize disordered protein strongly shape protein interactomes. An important scaffold of this type that contributes to transcription is the TFIIS N-terminal domain (TND). The TND is a five-helical bundle that has no known enzymatic activity, but instead selectively reads intrinsically disordered sequences of other proteins. Here, we review the structural and functional properties of TNDs and their cognate disordered ligands known as TND-interacting motifs (TIMs). TNDs or TIMs are found in prominent members of the transcription machinery, including TFIIS, super elongation complex, SWI/SNF, Mediator, IWS1, SPT6, PP1-PNUTS phosphatase, elongin, H3K36me3 readers, the transcription factor MYC, and others. We also review how the TND interactome contributes to the regulation of transcription. Because the TND is the most significantly enriched fold among transcription elongation regulators, TND- and TIM-driven interactions have widespread roles in the regulation of many transcriptional processes.

Keywords: intrinsically disordered proteins; molecular scaffolds; structural biology; transcription.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Elongin / metabolism
  • Gene Expression Regulation
  • Transcription Factors* / metabolism
  • Transcriptional Elongation Factors* / chemistry
  • Transcriptional Elongation Factors* / genetics
  • Transcriptional Elongation Factors* / metabolism

Substances

  • transcription factor S-II
  • Transcription Factors
  • Transcriptional Elongation Factors
  • Elongin