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

Yin, Zhou; Machius, Mischa; Nestler, Eric J.; Rudenko, Gabby

doi:10.1093/nar/gkx795

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

Journal Article · Thu Sep 07 00:00:00 EDT 2017 · Nucleic Acids Research

DOI:https://doi.org/10.1093/nar/gkx795· OSTI ID:1409105

Yin, Zhou ^[1]; Machius, Mischa ^[1]; Nestler, Eric J. ^[2]; Rudenko, Gabby ^[1]

Texas A & M Univ. at Galveston, TX (United States)
Icahn School of Medicine at Mount Sinai, New York, NY (United States)

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.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: R01 DA040621

OSTI ID:: 1409105

Journal Information:: Nucleic Acids Research, Vol. 45, Issue 19; ISSN 0305-1048

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 32 works

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