How hormone receptor DNA binding affects nucleosomal DNA: The role of symmetry

被引:19
作者
Bishop, TC
Kosztin, D
Schulten, K
机构
[1] UNIV ILLINOIS, BECKMAN INST 3147, DEPT PHYS, URBANA, IL 61801 USA
[2] UNIV ILLINOIS, BECKMAN INST, DEPT CHEM, URBANA, IL 61801 USA
关键词
D O I
10.1016/S0006-3495(97)78849-0
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
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-Angstrom 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.
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页码:2056 / 2067
页数:12
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