The ancillary N-terminal region of the yeast AP-1 transcription factor Yap8 contributes to its DNA binding specificity

Abstract

<jats:title>ABSTRACT</jats:title><jats:p>Activator protein 1 (AP-1) is one of the largest families of basic leucine zipper (bZIP) transcription factors in eukaryotic cells. How AP-1 proteins achieve target DNA binding specificity remains elusive. In <jats:italic>Saccharomyces cerevisiae</jats:italic>, the AP-1-like protein (Yap) family comprises eight members (Yap1 to Yap8) that display distinct genomic target sites despite high sequence homology of their DNA binding bZIP domains. In contrast to the other members of the Yap family, which preferentially bind to short (7-8 bp) DNA motifs, Yap8 binds to an unusually long DNA motif (13 bp). It has been unclear what determines this unique specificity of Yap8. In this work, we use molecular and biochemical analysis combined with computer-based structural design and molecular dynamics simulations of Yap8-DNA interactions to better understand the structural basis of DNA binding specificity determinants. We identify specific residues in the N-terminal tail preceding the basic region, which define stable association of Yap8 with the <jats:italic>ACR3</jats:italic> promoter. We propose that the N-terminal tail directly interacts with DNA and stabilizes Yap8 binding to the 13 bp motif. Thus, beside the core basic region, the adjacent N-terminal region contributes to alternative DNA binding selectivity within the AP-1 family.</jats:p>

Caracterização estrutural do polimorfismo -964G<A na interação do fator de transcrição HIF1 com seu elemento regulatório na região promotora do gene HLA-G

“…An energy minimization for 0.1 nanoseconds (ns) was carried out to eliminate bad contacts between the atoms, followed by an equilibration step with number of particles, volume, and temperature constants (NVT) and another with number of particles, pressure, and temperature constant (NPT). MD simulations were carried out at constant pressure and temperature (1 atm and 300 K) per 200 ns 57 . Structural analyses deviation such as RMSD, root mean square fluctuations (RMSF) and raddi of gyration (RoG) were done from MD trajectories.…”