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

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

Nucleic Acids Res. 2017 Nov 2;45(19):11425-11436.
doi: 10.1093/nar/gkx795.

 

© 2017 Oxford University Press.

  Yin Z, Machius M, Nestler EJ, Rudenko G.

Another SBC Highlight:

Structure analyses reveal a regulated oligomerization mechanism of the PlexinD1/GIPC/myosin VI complex

Structural determinants of APOBEC3B non-catalytic domain for molecular assembly and catalytic regulation

 

 

Nucleic Acids Res. 2017 Jul 7;45(12):7494-7506.
doi: 10.1093/nar/gkx362.

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When completing your Experimental Safety Approval Form (ESAF), please include the following in your experimental description:

 

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A robot is available for use at beamline 19-BM. The sample dewar accommodates ten Unipuck magazines; pins must be 18mm in length and use either SSRL or ALS bases. Experienced users may now request remote access to 19-BM when applying for beamtime.

 

 

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The on-line SBC Beamtime Request System allows users to view available beamtime on 19-ID and 19-BM, and to submit a request for rapid beamtime allocation.

Beamtime is available to the research community via a peer reviewed proposal system; it is supported by the U.S. Department of Energy, Office of Biological and Environmental Research.

Current Beamline Statistics:

APS PDB Depositions from BioSync
SBC Sector 19 2015 2016 2017 TOTAL
ID BM ID BM ID BM
PDB Depositions 259 32 228 29 169 28 5187

APS Publications Database:

Publications Total
SBC-CAT Publication List: 19-ID 1555
SBC-CAT Publication List: 19-BM 544
SBC-CAT Publication List: ALL
APS Publications Database

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MCSG's structure determination platform is well established, and combines technologies, robotics and expertise for gene cloning, protein production, and crystallization, as well as biochemical and biophysical characterization.

 

For further information, please contact Andrzej Joachimiak.

 

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CCP4 Study Weekend

January 11-12, 2018

Nottingham; East Midlands, England; UK

 

Protein Society's 32nd Annual Symposium

July 09-12, 2018

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American Crystallographic Association: 2018

July 20-24, 2018

Toronto; Ontario, Canada

 

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19-ID Beamline Cordless Phone 630-252-0569
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