Naslov
Biophysical studies of the hormone-binding domain of the estrogen receptor

Autori
Luck, Linda A. ; Swartz, Derrick J. ; Maab, Angela ; Salopek-Sondi, Branka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Proceedings, Volume 1 / N. N. - Washington (MD) : U. S. Army Medical Research and Materiel Command, 2002, P7-17

Skup
Era of Hope Department of Defense Breast Cancer Research Program Meeting

Mjesto i datum
Orlando (FL), Sjedinjene Američke Države, 25.09.2002. - 28.09.2002

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
estrogen; receptor; fluorine NMR; breast cancer

Sažetak
Hormones such as estrogen normally regulate the growth of human breast cells. This hormone binds to specific estrogen receptors that are present in about 70% of breast cancers at diagnosis. The estrogen receptor has four distinct actions, which modulate biological activity: (1) binding hormone (2) forming multimeric complexes (3) binding to sequence specific DNA and (4) modulating transcription. The key event, which is accomplished by the hormone-binding domain, is the interaction with ligand. After binding the ligand the estrogen receptor subsequently undergoes a conformational change leading to the cascade of events culminating in transcription and subsequent protein production. Our laboratory is interested in studying the hormone-binding domain of the estrogen receptor because it contains the regulatory actions of the protein. The hormone-binding domain is responsible for its own action of ligand binding and conformational change. Thus the interplay between the ligand and the binding domain may carefully select how the biologies are manifested. In addition, this domain has been known to be very promiscuous in its ligand binding action. Structually unrelated molecules, known as xenoestrogens, bind to the protein. These environmental agents mimic the effects of the naturally occurring hormone and may be responsible for adverse health consequences in women. We are using a combination of biophysical methods and genetic engineering to examine the hormone-binding domain to provide insight into the mechanisms of action of estrogens, antiestrogens and hormone disrupting agents. Fluorine NMR has been exploited to demonstrate conformational changes in the protein along with selectivity in ligand binding. Urea denaturation using fluorescence allowed us to look at ligand-induced structural stability of the hormone binding domain.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

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