Accession Number : ADA337505

Title :   Structure/Function of Recombinant Human Estrogen Receptor.

Descriptive Note : Annual rept. 1 Sep 96-31 Aug 97

Corporate Author : CALIFORNIA UNIV IRVINE

Personal Author(s) : Vickery, Larry E.

PDF Url : ADA337505

Report Date : SEP 1997

Pagination or Media Count : 32

Abstract : Interaction of the estrogen receptor with its ligands is mediated by a C-terminal region of the protein designated the hormone binding domain (HBD). Extensive, unsuccessful, attempts were made to crystallize the protein. In the absence of structural data, we performed homology modeling of the HBD. One prediction of the model was the formation of an intrachain disulfide bond; however, no experimental evidence for the existence of the bond was found. The HBD did form disulfide bonds between peptides, supporting the prediction of either one or two surface exposed cysteine residues. Previous studies indicated that the dissociation of the HBD dimer in solution is a slow process with a half-life of 1-2 hours, which ligand binding increased 3-fold (estradiol) to 4-fold (4-hydroxytamoxifen). HBD constructs with altered N-termini exhibited some differences in concentrations required for cooperativity and larger differences in dissociation half-life; others with only minor differences were found to be unstable. These results suggest that the N-terminus of the HBD contributes to folding of the protein and to dimer interactions.

Descriptors :   *COMPUTER PROGRAMS, *HORMONES, *COMMUNICATION TERMINALS, *ESTROGENS, *BREAST CANCER, FUNCTIONS, PREDICTIONS, HUMANS, INTERACTIONS, STRUCTURAL PROPERTIES, PEPTIDES, PROTEINS, LIGANDS, BONDING, DISSOCIATION, SULFIDES, FOLDING, SENSE ORGANS, DIMERS, HALF LIFE.

Subject Categories : Anatomy and Physiology
      Medicine and Medical Research
      Computer Programming and Software

Distribution Statement : APPROVED FOR PUBLIC RELEASE