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The bZIP dimer localizes at DNA full-sites where each basic region can alternately translocate and bind to subsites at the half-site.

Crystal structures of the GCN4 bZIP (basic region/leucine zipper) with the AP-1 or CRE site show how each GCN4 basic region binds to a 4 bp cognate half-site as a single DNA target; however, this may not always fully describe how bZIP proteins interact with their target sites. Previously, we showed that the GCN4 basic region interacts with all 5 bp in half-site TTGCG (termed 5H-LR) and that 5H-LR comprises two 4 bp subsites, TTGC and TGCG, which individually are also target sites of the basic region. In this work, we explore how the basic region interacts with 5H-LR when the bZIP dimer localizes to full-sites. Using AMBER molecular modeling, we simulated GCN4 bZIP complexes with full-sites containing 5H-LR to investigate in silico the interface between the basic region and 5H-LR. We also performed in vitro investigation of bZIP-DNA interactions at a number of full-sites that contain 5H-LR versus either subsite: we analyzed results from DNase I footprinting and electrophoretic mobility shift assay (EMSA) and from EMSA titrations to quantify binding affinities. Our computational and experimental results together support a highly dynamic DNA-binding model: when a bZIP dimer localizes to its target full-site, the basic region can alternately recognize either subsite as a distinct target at 5H-LR and translocate between the subsites, potentially by sliding and hopping. This model provides added insights into how α-helical DNA-binding domains of transcription factors can localize to their gene regulatory sequences in vivo.

Pubmed ID: 22856882


  • Chan IS
  • Al-Sarraj T
  • Shahravan SH
  • Fedorova AV
  • Shin JA



Publication Data

August 21, 2012

Associated Grants

  • Agency: NIGMS NIH HHS, Id: R01 GM069041
  • Agency: NIGMS NIH HHS, Id: R01GM069041

Mesh Terms

  • Base Sequence
  • Basic-Leucine Zipper Transcription Factors
  • Binding Sites
  • CCAAT-Enhancer-Binding Proteins
  • DNA Footprinting
  • DNA-Binding Proteins
  • Hydrogen Bonding
  • Saccharomyces cerevisiae Proteins