title: Truncated variants of the GCN4 transcription activator protein bind DNA with dramatically different dynamical motifs.
abstract: The yeast protein GCN4 is a transcriptional activator in the basic leucine zipper (bZip) family, whose distinguishing feature is the "chopstick-like" homodimer of alpha helices formed at the DNA-binding interface. While experiments have shown that truncated versions of the protein retain biologically relevant DNA-binding affinity, we present the results of a computational study revealing that these variants show a wide variety of dynamical modes in their interaction with the target DNA sequence. We have performed all-atom molecular dynamics simulations of the full-length GCN4 protein as well as three truncated variants; our data indicate that the truncated mutants show dramatically different correlation patterns. We conclude that although the truncated mutants still retain DNA-binding ability, the bZip interface present in the full-length protein provides important stability for the protein-DNA complex.
authors.affiliation: Department of Chemistry and Biochemistry, Utica College , 1600 Burrstone Road, Utica, New York 13502, United States.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: McHarris
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Barr
mesh_terms: D000595:Amino Acid Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D004271:DNA, Fungal / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013816:Thermodynamics; D014158:Transcription, Genetic
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D004271:DNA, Fungal; C501391:GCN4 protein, S cerevisiae; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins