ISSN:
0887-3585
Schlagwort(e):
receptor proteins
;
estrogen receptor
;
DNA bending
;
DNA unwinding
;
DNA recognition
;
molecular dynamics
;
Chemistry
;
Biochemistry and Biotechnology
Quelle:
Wiley InterScience Backfile Collection 1832-2000
Thema:
Medizin
Notizen:
Molecular dynamics simulations have been conducted to investigate the binding of the glucocorticoid receptor (GR) dimer to DNA. For this purpose simulations of the complex formed by a DNA segment and a dimer of GR-DNA binding domains (GR-DBD) have been carried out, employing an available X-ray structure. A second set of simulations was based on this structure as well, except that the DNA segment was altered to the consensus glucocorticoid response element (GRE). Simulations of a single GR-DBD and of the uncomplexed GRE served as controls. For the simulations, each system was encapsulated in an ellipsoid of water. Protein-DNA interactions, dimer interactions, and DNA structural parameters were analyzed for each system and compared. The consensus GRE is found to yield more favorable and symmetric interactions between the GR-DBDs and the GRE, explaining the ability of the GR dimer to recognize this DNA segment. Further analysis focused on deformations of the DNA that are induced by the binding of GR. The deformations observed involve a 35° bend of the DNA, an unwinding, and a displacement of the helical axis. These deformations are consistent with a mechanism for transcriptional regulation that involves a change of nucleosome packing upon GR binding. Significant protein-protein and protein-DNA interactions, both direct and water mediated, develop due to the deformations of the GRE and are indicative of an increased recognition achieved through DNA deformation. The interactions include direct interactions between the GRE and glycine-458 and serine-459, side groups which differentiate GR from other members of the nuclear hormone receptor family.
Zusätzliches Material:
15 Ill.
Materialart:
Digitale Medien
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