A ligand-induced conformational change in the estrogen receptor is localized in the steroid binding domain.
A ligand-induced conformational change in the estrogen receptor is localized in the steroid binding domain.
复制标题
雌激素受体中配体诱导的构象变化位于类固醇结合域中。
DOI：
10.1021/bi00138a009
复制
发表时间：
1992
期刊：
影响因子：
2.9
通讯作者：
Gorski,J
中科院分区：
文献类型：
--
作者：
Fritsch,M;Leary,CM;Furlow,JD;Ahrens,H;Schuh,TJ;Mueller,GC;Gorski,J
Revised Manuscript Received March 24, 1992 abstract: Upon binding estrogen, the estrogen receptor (ER) is proposed to undergo some form of conformational transition leading to increased transcription from estrogen-responsive genes. In vitro methods used to study the transition often do not separate heat-induced effects on the ER from estrogen-induced effects. The technique of affinity partitioning with PEG-palmitate was used to study the change in the hydrophobic surface properties of the ER upon binding ligand with and without in vitro heating. Upon binding estradiol (E2), the full-length rat uterine cytosolic ER undergoes a dramatic decrease in surface hydrophobicity. The binding of the anti-estrogen 4-hydroxytamoxifen (4-OHT) results in a similar decrease in surface hydrophobicity. These effects are independent of any conformational changes induced by heating the ER to 30 C for 45 min. The use of the human ER steroid binding domain overproduced in Escherichia coli (ER-C) and the trypsin-generated steroid binding domain from rat uterine cytosolic ER demonstrates that the decrease in surface hydrophobicity upon binding E2 or 4-OHT is localized to the steroid binding domain. Gel filtration analysis indicates that the change in surface hydrophobicity upon binding ligand is an inherent property of the steroidbinding domain and not due to a ligand-induced change in the oligomeric state of the receptor. The decrease in surface hydrophobicity of the steroid binding domain of the ER upon binding E2 or 4-OHT represents an early and possibly a necessary event in estrogen action and may be important for “tight” binding of the ER in the nucleus. e steroid receptor superfamily of DNA binding, nuclear transcription factors includes the estrogen receptor (ER) 1 (Evans, 1988). Early studies usingcontrolled proteolysis as tThis work was supported in part by the College of Agricultural and Life Sciences, University of Wisconsin—Madison, by NIH Grants HD07259 and HD08192 awarded to JG, and by Fellowship PRTF-107 awarded to MF from the AmericanCancer Society.* To whom correspondence shouldbe addressed.'Department of Biochemistry. I Present address: Clinical Sciences Center, University of Wisconsin.* McArdle Laboratory for Cancer Research. II Present address: Department of Biochemistry, University of Wash-ington, Seattle, WA 98195. well as more recent cloning of the cDNA for the ER have revealed distinct functional domains (Green et al., 1986; 1 Abbreviations: ER, estrogen receptor; hsp, heat shock protein; ERE, estrogen response element; E2, estradiol; 4-OHT, 4-hydroxytamoxifen; PEG, poly (ethylene glycol); ATPP, aqueous two-phase partitioning; PMSF, phenylmethanesulfonyl fluoride; HAP, hydroxylapatite; EDTA, ethylenediaminetetraacetic acid; BCIP, 5-bromo-4-chloro-3-indolyl 1-phosphate; NBT, nitro blue tetrazolium; U, unoccupied ER; EO, E2-occupied ER; AO, 4-OHT-occupied ER; UH, unoccupied heated ER; EOH, E2-occupied heated ER; AOH, 4-OHT-occupied heated ER; DES, diethylstilbestrol; SDS, sodium dodecyl sulfate; PAGE, polyacrylamide gel electrophoresis; DTT, dithiothreitol; TAMZ, tamoxifen aziridine; K0, void volume; SEM, standard error of the mean; kDa, kilodalton (s).
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DOI：
10.1210/mend-4-11-1704
发表时间：
1990
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
--
作者：
Smith,DF;Schowalter,DB;Kost,SL;Toft,DO
通讯作者：
Toft,DO
尿素和盐稳定的 DNA 结合雌激素受体二聚体的独特分子特性，共价标记有抗雌激素 [3H] 去甲基萘福昔定氮丙啶。
影响因子：
--
作者：
T. Hutchens;R. W. McNaught;T. Yip;T. Suzuki;C. Li;P. Besch
通讯作者：
P. Besch
DOI：
--
发表时间：
1976
期刊：
European Journal of Biochemistry
影响因子：
--
作者：
C. Axelsson;V. Shanbhag
通讯作者：
V. Shanbhag
子宫雌激素受体的两种高亲和力配体结合状态通过疏水环境的调节来区分。
影响因子：
2.9
作者：
T. Hutchens;C. Li;N. Zamah;P. Besch
通讯作者：
P. Besch
通过水性两相聚合物体系中的分配确定 β-乳球蛋白的结构和疏水表面性质的变化。
DOI：
10.1016/0005-2795(78)90544-5
发表时间：
1978
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
C. Axelsson
通讯作者：
C. Axelsson