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Structural elements of an orphan nuclear receptor-DNA complex.

Zhao Q, Khorasanizadeh S, Miyoshi Y, Lazar MA, Rastinejad F
Mol Cell 1 849-61 (1998)
Cited: 93 times
EuropePMC logo PMID: 9660968

Abstract

The nuclear hormone receptors form the largest known family of transcription factors. The current notion of receptor DNA discrimination, based solely on one major type of hexameric half-site and a highly conserved 66-residue core DNA-binding domain (DBD), does not adequately describe how more than 150 nonsteroid receptors differentiate among response elements. Here, we describe the 2.3 A crystal structure of the DNA-binding region of the orphan receptor RevErb arranged as a tandem homodimer on its optimal response element. The structure reveals the presence of a second major protein-DNA interface adjacent to the classical one involving the half-sites. A sequence comparison of orphan receptors suggests that unique minor-groove interactions involving the receptor hinge regions impart the necessary DNA and dimerization specificity.

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