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.

Center for Cancer Epigenetics The University of Texas MD Anderson Cancer Center Houston TX U S A

Dan L Duncan Comprehensive Cancer Center Baylor College of Medicine Houston TX U S A

Department of Bioengineering Rice University Houston TX U S A

Department of Cell Biology Faculty of Science Charles University Prague Czech Republic

Department of Molecular and Cellular Biology Center for Precision Environmental Health Baylor College of Medicine Houston TX U S A

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Prague Czech Republic

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