Abstract
Activator protein-1 (AP-1) comprises one of the largest and most evolutionary conserved families of ubiquitous eukaryotic transcription factors that act as a pioneer factor. Diversity in DNA binding interaction of AP-1 through a conserved basic-zipper (bZIP) domain directs in-depth understanding of how AP-1 achieves its DNA binding selectivity and consequently gene regulation specificity. Here, we address the structural and dynamical aspects of the DNA target recognition process of AP-1 using microsecond-long atomistic simulations based on the structure of the human AP-1 FosB/JunD bZIP-DNA complex. Our results show the unique role of DNA shape features in selective base specific interactions, characteristic ion population, and solvation properties of DNA grooves to form the motif sequence specific AP-1-DNA complex. The TpG step at the two terminals of the AP-1 site plays an important role in the structural adjustment of DNA by modifying the helical twist in the AP-1 bound state. We addressed the role of intrinsic motion of the bZIP domain in terms of opening and closing gripper motions of DNA binding helices, in target site recognition and binding of AP-1 factors. Our observations suggest that binding to the cognate motif in DNA is mainly accompanied with the precise adjustment of closing gripper motion of DNA binding helices of the bZIP domain.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.