6ZV4

Human TFIIS N-terminal domain in complex with IWS1

Summary for 6ZV4

• Entry DOI: 10.2210/pdb6zv4/pdb
• NMR Information: BMRB: 34541
• Descriptor: Transcription elongation factor A protein 1,Protein IWS1 homolog (1 entity in total)
• Functional Keywords: transcription elongation, transcription
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 1
• Total formula weight: 12600.16

Authors

Veverka, V. (deposition date: 2020-07-23, release date: 2021-12-01, Last modification date: 2024-06-19)

Primary citation

Cermakova, K.,Demeulemeester, J.,Lux, V.,Nedomova, M.,Goldman, S.R.,Smith, E.A.,Srb, P.,Hexnerova, R.,Fabry, M.,Madlikova, M.,Horejsi, M.,De Rijck, J.,Debyser, Z.,Adelman, K.,Hodges, H.C.,Veverka, V.
A ubiquitous disordered protein interaction module orchestrates transcription elongation.
Science, 374:1113-1121, 2021

PubMed Abstract: During eukaryotic transcription elongation, RNA polymerase II (RNAP2) is regulated by a chorus of factors. Here, we identified a common binary interaction module consisting of TFIIS N-terminal domains (TNDs) and natively unstructured TND-interacting motifs (TIMs). This module was conserved among the elongation machinery and linked complexes including transcription factor TFIIS, Mediator, super elongation complex, elongin, IWS1, SPT6, PP1-PNUTS phosphatase, H3K36me3 readers, and other factors. Using nuclear magnetic resonance, live-cell microscopy, and mass spectrometry, we revealed the structural basis for these interactions and found that TND-TIM sequences were necessary and sufficient to induce strong and specific colocalization in the crowded nuclear environment. Disruption of a single TIM in IWS1 induced robust changes in gene expression and RNAP2 elongation dynamics, which underscores the functional importance of TND-TIM surfaces for transcription elongation.

PubMed: 34822292
DOI: 10.1126/science.abe2913

Experimental method

SOLUTION NMR