title: How hormone receptor-DNA binding affects nucleosomal DNA: the role of symmetry.
abstract: Molecular dynamics simulations have been employed to determine the optimal conformation of an estrogen receptor DNA binding domain dimer bound to a consensus response element, ds(AGGTCACAGTGACCT), and to a nonconsensus response element, ds(AGAACACAGTGACCT). The structures simulated were derived from a crystallographic structure and solvated by a sphere (45-A radius) of explicit water and counterions. Long-range electrostatic interactions were accounted for during 100-ps simulations by means of a fast multipole expansion algorithm combined with a multiple time-step scheme in the molecular dynamics package NAMD. The simulations demonstrate that the dimer induces a bent and underwound (10.7 bp/turn) conformation in the DNA. The bending reflects the dyad symmetry of the receptor dimer and can be described as an S-shaped curve in the helical axis of DNA when projected onto a plane. A similar bent and underwound conformation is observed for nucleosomal DNA near the nucleosome's dyad axis that reflects the symmetry of the histone octamer. We propose that when a receptor dimer binds to a nucleosome, the most favorable dimer-DNA and histone-DNA interactions are achieved if the respective symmetry axes are aligned. Such positioning of a receptor dimer over the dyad of nucleosome B in the mouse mammary tumor virus promoter is in agreement with experiment.
authors.affiliation: Beckman Institute, Department of Chemistry, University of Illinois at Urbana-Champaign 61801, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Bishop
authors.forename: D
authors.initials: D
authors.lastname: Kosztin
authors.forename: K
authors.initials: K
authors.lastname: Schulten
mesh_terms: D004268:DNA-Binding Proteins / Q000737:chemistry*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D008956:Models, Chemical; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000737:chemistry*; D011956:Receptors, Cell Surface / Q000737:chemistry*
chemical_list: D004268:DNA-Binding Proteins; D009707:Nucleosomes; D011956:Receptors, Cell Surface