5VPE

Transcription factor FosB/JunD bZIP domain in complex with cognate DNA, type-I crystal

Summary for 5VPE

• Entry DOI: 10.2210/pdb5vpe/pdb
• Related: 5VPA 5VPB 5VPC 5VPD 5VPF
• Descriptor: Protein fosB, Transcription factor jun-D, DNA (5'-D(*CP*GP*TP*CP*GP*GP*TP*GP*AP*CP*TP*CP*AP*CP*CP*GP*AP*CP*G)-3'), ... (9 entities in total)
• Functional Keywords: activator protein-1, basic leucine zipper, bzip, fos, jun, transcription factor, dna-binding protein, redox switch, coiled-coil, transcription-dna complex, transcription/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 56892.56

Authors

Yin, Z.,Machius, M.,Rudenko, G. (deposition date: 2017-05-04, release date: 2017-09-06, Last modification date: 2023-10-04)

Primary citation

Yin, Z.,Machius, M.,Nestler, E.J.,Rudenko, G.
Activator Protein-1: redox switch controlling structure and DNA-binding.
Nucleic Acids Res., 45:11425-11436, 2017

PubMed 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.

PubMed: 28981703
DOI: 10.1093/nar/gkx795

Experimental method

X-RAY DIFFRACTION (2.053 Å)