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On the mechanism of DNA binding by nuclear hormone receptors: A structural and functional perspective
Author(s) -
Freedman Leonard P.,
Luisi Ben F.
Publication year - 1993
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240510205
Subject(s) - nuclear receptor , receptor , pelp 1 , biology , zinc finger , dna binding domain , nuclear receptor coactivator 1 , computational biology , estrogen receptor , small heterodimer partner , dna , mechanism (biology) , glucocorticoid receptor , genetics , microbiology and biotechnology , gene , transcription factor , physics , quantum mechanics , cancer , breast cancer
The nuclear hormone receptor DNA‐binding domain consists of two zinc finger‐like modules whose amino acids are highly conserved among the members of the receptor superfamily. In this review, we describe the various genetic, biochemical, and structural experiments that have been carried out primarily for the DNA‐binding domains of the glucocorticoid and estrogen receptors. We describe how the structural and functional information have permitted us to predict properties of the DNA‐binding domains of other nuclear receptors. We postulate how receptors discriminate closely related response elements through sequence‐specific contacts and distinguish symmetry of target sites through protein‐protein interactions. This mechanism explains in part how the receptors regulate diverse sets of genes from a limited repertoire of core response elements. Lastly, we describe the stereochemical basis of nuclear receptor dysfunction in certain clinical disorders. © 1993 Wiley‐Liss, Inc.