Activator Protein-1: redox switch controlling structure and DNA-binding. Issue 19 (7th September 2017)

• Record Type: Journal Article
• Authors: Yin, Zhou; Machius, Mischa; Nestler, Eric J.; Rudenko, Gabby
• Is Part Of: Nucleic acids research. Volume 45:Issue 19(2017)
• Page Start: 11425
• Page End: 11436
• Publication Date: 2017-09-07
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkx795
• Languages: English
• ISSNs: 0305-1048

Abstract

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.