Summary information and primary citation

PDB-id
5vpe; DSSR-derived features in text and JSON formats
Class
transcription-DNA
Method
X-ray (2.053 Å)
Summary
Transcription factor fosb-jund bzip domain in complex with cognate DNA, type-i crystal
Reference
Yin Z, Machius M, Nestler EJ, Rudenko G (2017): "Activator Protein-1: redox switch controlling structure and DNA-binding." Nucleic Acids Res., 45, 11425-11436. doi: 10.1093/nar/gkx795.
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.

Cartoon-block schematics in six views (download the tarball)

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