AP-1 (Activating Protein-1) is a collective term referring to dimeric TFs composed of Jun, Fos or ATF subunits that bind to the AP-1 binding site on DNA. This interaction is integral to regulating important cellular processes such as differentiation, proliferation and apoptosis.
The FosB/JunD heterodimer contains two inter-coiled helices held together by a leucine zipper and two helical basic regions that interact with the DNA major grooves. It was previously thought that in the absence of DNA, bZIP proteins were unfolded and only adopted a helical structure upon DNA binding, but the crystallisation of FosB/JunD proves otherwise.
Even in the absence of DNA, the conformation of JunD allows for DNA binding but the FosB is still required to undergo a large conformational change. This is controlled by a ‘redox switch’ mediated by an inter-molecular cysteine disulfide bond between JunD and FosB. This discovery has implications in designing therapeutics targeted towards the binding of AP-1.
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