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Activator Protein-1: redox switch controlling structure and DNA-binding.
Yin, Zhou; Machius, Mischa; Nestler, Eric J; Rudenko, Gabby.
Afiliación
  • Yin Z; Department of Pharmacology and Toxicology, and the Sealy Center for Structural Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Machius M; Department of Pharmacology and Toxicology, and the Sealy Center for Structural Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Nestler EJ; Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, New York, NY 10029, USA.
  • Rudenko G; Department of Pharmacology and Toxicology, and the Sealy Center for Structural Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Nucleic Acids Res ; 45(19): 11425-11436, 2017 Nov 02.
Article en En | MEDLINE | ID: mdl-28981703
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN / Proteínas Proto-Oncogénicas c-jun / Factor de Transcripción AP-1 / Dominios Proteicos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nucleic Acids Res Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN / Proteínas Proto-Oncogénicas c-jun / Factor de Transcripción AP-1 / Dominios Proteicos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nucleic Acids Res Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido