The TFIIS N-Terminal Domain (TND): A Transcription Assembly Module at the Interface of Order and Disorder

Authors

Katerina Cermakova
Vaclav Veverka
H Courtney Hodges

Publication Date

2-27-2023

Journal

Biochemical Society Transactions

DOI

10.1042/BST20220342

PMID

36651856

PMCID

PMC9987994

PubMedCentral® Posted Date

1-18-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Transcription Factors, Transcriptional Elongation Factors, Elongin, Gene Expression Regulation, intrinsically disordered proteins, molecular scaffolds, structural biology, transcription

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.