A metal-linked gapped zipper model is proposed for the 90 kDa heat shock protein-estrogen receptor interface.
A novel arrangement is proposed for the association of the 90 kDa heat shock protein (hsp 90) dimer and the human estrogen receptor (hER) monomer. Secondary structure analyses of the hsp 90 molecule reveal the presence of a cysteine-containing, leucine-rich, heptad repeat, which we refer to as region C. Similar analyses on the hER, at its hormone binding domain (HBD), have indicated the presence of a central subdomain bordered by 2 alpha-helical flanking segments which also display the heptad substructure. Due to its predicted potential for conformational change (1) we refer to this central subdomain as the Helix Conversion Unit or HCU. It contains an HX5C peptide and shares significant homology with the metal-binding domain of a gag-encoded HIV-LAV protein (2). We predict that, by virtue of its presence in duplicate, region C may be capable of simultaneous leucine zipper-like pairing with the hER at its flanking helices, as well as the formation of a shared CCHC-box-type metal binding link with the same hER at the putative HCU which lies in between.
Schwartz
J A
JA
Department of Biological Sciences, Wayne State University, Detroit, Michigan 48202.
Mizukami
H
H
D000595:Amino Acid Sequence; D001665:Binding Sites; D006360:Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008956:Models, Chemical; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011960:Receptors, Estrogen / Q000737:chemistry* / Q000378:metabolism
D006360:Heat-Shock Proteins; D011960:Receptors, Estrogen