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Science 21 May 1993:
Vol. 260. no. 5111, pp. 1117 - 1121
DOI: 10.1126/science.8388124
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Articles

Science, Vol 260, Issue 5111, 1117-1121
Copyright © 1993 by American Association for the Advancement of Science

articles

Structure of the retinoid X receptor alpha DNA binding domain: a helix required for homodimeric DNA binding

MS Lee, SA Kliewer, J Provencal, PE Wright, and RM Evans

Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037.

The three-dimensional solution structure of the DNA binding domain (DBD) of the retinoid X receptor alpha (RXR alpha) was determined by nuclear magnetic resonance spectroscopy. The two zinc fingers of the RXR DBD fold to form a single structural domain that consists of two perpendicularly oriented helices and that resembles the corresponding regions of the glucocorticoid and estrogen receptors (GR and ER, respectively). However, in contrast to the DBDs of the GR and ER, the RXR DBD contains an additional helix immediately after the second zinc finger. This third helix mediates both protein-protein and protein-DNA interactions required for cooperative, dimeric binding of the RXR DBD to DNA. Identification of the third helix in the RXR DBD thus defines a structural feature required for selective dimerization of the RXR on hormone response elements composed of half-sites (5'-AGGTCA-3') arranged as tandem repeats.


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