Activator protein-1: Redox switch controlling structure and DNA-binding

Zhou Yin, Mischa Machius, Eric J. Nestler, Gabby Rudenko

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The transcription factor, activator protein-1 (AP-1), binds to cognate DNA under redox control; yet, the underlying mechanism has remained enigmatic. A series of crystal structures of the AP-1 FosB/JunD bZIP domains reveal ordered DNA-binding regions in both FosB and JunD even in absence DNA. However, while JunD is competent to bind DNA, the FosB bZIP domain must undergo a large conformational rearrangement that is controlled by a 'redox switch' centered on an inter-molecular disulfide bond. Solution studies confirm that FosB/JunD cannot undergo structural transition and bind DNA when the redox-switch is in the 'OFF' state, and show that the mid-point redox potential of the redox switch affords it sensitivity to cellular redox homeostasis. The molecular and structural studies presented here thus reveal the mechanism underlying redox-regulation of AP-1 Fos/Jun transcription factors and provide structural insight for therapeutic interventions targeting AP-1 proteins.

Original languageEnglish (US)
Pages (from-to)11425-11436
Number of pages12
JournalNucleic acids research
Volume45
Issue number19
DOIs
StatePublished - 2017

ASJC Scopus subject areas

  • Genetics

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