A metal-linked gapped zipper model is proposed for the hsp90-glucocorticoid receptor interaction.
In the presence of certain metals, regions of the hormone binding domain of the glucocorticoid receptor (GR) are capable of binding the 90 kDa heat shock protein (hsp90). Using secondary structure prediction methods in correlation with the experimental data, we propose a model which predicts the presence of two widely spaced leucine zipper-like heptads on either side of a central subdomain. The heptads could interact hydrophobically with similar regions on the hsp90 homodimer, bringing putative metal binding residues on each protein close enough to establish a shared metal bridge. The central subdomain between heptads is suggested to contain regions involved in metal binding, steroid binding, and conformational mobility. The hypothetical model that we are proposing therefore addresses the nature of the structural link between hsp90 binding, hormone binding, and conformational changes in the receptor.
Schwartz
J A
JA
Department of Physiology, School of Medicine, Wayne State University, Detroit, MI 48201.
Mizukami
H
H
Skafar
D F
DF
D000595:Amino Acid Sequence; D001665:Binding Sites; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D016350:Leucine Zippers; D046911:Macromolecular Substances; D008667:Metalloproteins / Q000737:chemistry; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011965:Receptors, Glucocorticoid / Q000737:chemistry / Q000378:metabolism*
D006360:Heat-Shock Proteins; D046911:Macromolecular Substances; D008667:Metalloproteins; D011965:Receptors, Glucocorticoid