Chemical perturbation of an intrinsically disordered region of TFIID distinguishes two modes of transcription initiation.

Elife
Authors
Keywords
Abstract

Intrinsically disordered proteins/regions (IDPs/IDRs) are proteins or peptide segments that fail to form stable 3-dimensional structures in the absence of partner proteins. They are abundant in eukaryotic proteomes and are often associated with human diseases, but their biological functions have been elusive to study. In this study, we report the identification of a tin(IV) oxochloride-derived cluster that binds an evolutionarily conserved IDR within the metazoan TFIID transcription complex. Binding arrests an isomerization of promoter-bound TFIID that is required for the engagement of Pol II during the first (de novo) round of transcription initiation. However, the specific chemical probe does not affect reinitiation, which requires the re-entry of Pol II, thus, mechanistically distinguishing these two modes of transcription initiation. This work also suggests a new avenue for targeting the elusive IDRs by harnessing certain features of metal-based complexes for mechanistic studies, and for the development of novel pharmaceutical interventions.

Year of Publication
2015
Journal
Elife
Volume
4
Date Published
2015 Aug 28
ISSN
2050-084X
DOI
10.7554/eLife.07777
PubMed ID
26314865
PubMed Central ID
PMC4582147
Links
Grant list
RC2 CA148399 / CA / NCI NIH HHS / United States
Howard Hughes Medical Institute / United States
R01 CA160860 / CA / NCI NIH HHS / United States
N01CO12400 / CA / NCI NIH HHS / United States
N01-CO-12400 / CO / NCI NIH HHS / United States