Summary information and primary citation
- PDB-id
- 5vpe; SNAP-derived features in text and JSON formats;
DNAproDB
- 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.
