DNA target selectivity by the vitamin D(3) receptor: Mechanism of dimer binding to an asymmetric repeat element Journal Article


Authors: Towers, T. L.; Luisi, B. F.; Asianov, A.; Freedman, L. P.
Article Title: DNA target selectivity by the vitamin D(3) receptor: Mechanism of dimer binding to an asymmetric repeat element
Abstract: The 1,25-dihydroxyvitamin D3 receptor, like other members of the nuclear receptor superfamily, forms dimers in solution that are probably stabilized by a dyad symmetrical interface formed by the ligand-binding domain. This receptor, however, recognizes DNA targets that are not dyad symmetric but rather are organized as direct repeats of a hexameric sequence with a characteristic 3-bp spacing. Using molecular modeling and site-directed mutagenesis, we have identified regions within the vitamin D3 receptor zinc finger region that confer selectivity for direct repeats with appropriate spacing. Reflecting the organization of the DNA target, these regions, mapping to the tip of the first zinc finger module and the N and C termini of the second finger module, direct asymmetrical protein-protein contacts. A stereochemical model is proposed for these interactions.
Keywords: nonhuman; protein domain; carboxy terminal sequence; amino acid sequence; amino terminal sequence; dna sequence; protein secondary structure; dna binding; site directed mutagenesis; cell nucleus receptor; ligand binding; receptor binding; stereochemistry; dimer; repetitive dna; priority journal; article; calcitriol receptor
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 90
Issue: 13
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 1993-07-13
Start Page: 6310
End Page: 6314
Language: English
DOI: 10.1073/pnas.90.13.6310
PUBMED: 8392196
PROVIDER: scopus
PMCID: PMC46918
DOI/URL:
Notes: Article -- Export Date: 1 March 2019 -- Source: Scopus
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