PDBsum entry 5vpe

Transcription/DNA

PDB id: 5vpe

Contents

Protein chains

66 a.a.

67 a.a.

DNA/RNA

Ligands

PO4 ×3

EDO ×11

Metals

_NA ×3

_CL

Waters ×230

PDB id:

5vpe

Name:

Transcription/DNA

Title:

Transcription factor fosb/jund bzip domain in complex with cognate DNA, type-i crystal

Structure:

Protein fosb. Chain: c, a. Fragment: unp residues 153-219. Synonym: g0/g1 switch regulatory protein 3. Engineered: yes. Transcription factor jun-d. Chain: d, b. Fragment: unp residues 266-332. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: fosb, g0s3. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: jund. Synthetic: yes. Organism_taxid: 9606

Resolution:

2.05Å R-factor: 0.219 R-free: 0.254

Authors:

Z.Yin,M.Machius,G.Rudenko

Key ref:

Z.Yin et al. (2017). Activator Protein-1: redox switch controlling structure and DNA-binding. Nucleic Acids Res, 45, 11425-11436. PubMed id: 28981703

Date:

04-May-17 Release date: 06-Sep-17

Protein chains

P53539  (FOSB_HUMAN) -  Protein FosB from Homo sapiens

Seq: 338 a.a.

Struc: 66 a.a.

Protein chains

P17535  (JUND_HUMAN) -  Transcription factor JunD from Homo sapiens

Seq: 347 a.a.

Struc: 67 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DNA/RNA chains

G-T-C-G-G-T-G-A-C-T-C-A-C-C-G-A-C-G 18 bases

C-G-T-C-G-G-T-G-A-G-T-C-A-C-C-G-A-C 18 bases

G-T-C-G-G-T-G-A-C-T-C-A-C-C-G-A-C-G 18 bases

C-G-T-C-G-G-T-G-A-G-T-C-A-C-C-G-A-C 18 bases

Enzyme reactions

• Enzyme class: Chains C, D, A, B: E.C.?

Nucleic Acids Res 45:11425-11436 (2017)

PubMed id: 28981703

Activator Protein-1: redox switch controlling structure and DNA-binding.

Z.Yin, M.Machius, E.J.Nestler, G.Rudenko.

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.