Linked Life Data

12960019

Source:http://linkedlifedata.com/resource/pubmed/id/12960019

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2003-10-27
pubmed:abstractText
Nuclear hormone receptor-responsive element binding specificity has been reported to reside predominantly in the proximal box (P-box), three amino acids located in a DNA-recognition alpha-helix situated on the C-terminal side of the first zinc finger. To further define the residues in the vitamin D receptor (VDR) DNA binding domain (DBD) that mediate its interaction as a retinoid X receptor (RXR) heterodimer with the rat osteocalcin vitamin D-responsive element (VDRE), chimeric receptors were created in which the core DBD of VDR was replaced with that of the homodimerizing glucocorticoid receptor (GR). Systematic alteration of GR DBD amino acids in these chimeras to VDR DBD residues identified arg-49 and lys-53, just C-terminal of the P-box within the base recognition alpha-helix of human VDR (hVDR), as the only two amino acids among 36 differences required to convert the GR core zinc finger domain to that of the VDR. Gel mobility shift and 1,25-dihydroxyvitamin D3-stimulated transcription assays verified that an hVDR-GR DBD chimera is functional on the rat osteocalcin VDRE with only the conservative change of lys-49 to arg, and of the negatively charged glu-53 to a basic amino acid (lys or arg). Thus, for RXR heterodimerizing receptors like VDR, the P-box requires redefinition and expansion to include a DNA specificity element corresponding to arg-49 and lys-53 of hVDR. Examination of DNA specificity element amino acids in other nuclear receptors in terms of conservation and base contact in cocrystal structures supports the conclusion that these residues are crucial for selective DNA recognition.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
144
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5065-80
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12960019-Amino Acid Sequence, pubmed-meshheading:12960019-Amino Acid Substitution, pubmed-meshheading:12960019-Animals, pubmed-meshheading:12960019-COS Cells, pubmed-meshheading:12960019-Crystallography, pubmed-meshheading:12960019-DNA, pubmed-meshheading:12960019-Dimerization, pubmed-meshheading:12960019-Humans, pubmed-meshheading:12960019-Mice, pubmed-meshheading:12960019-Osteocalcin, pubmed-meshheading:12960019-Protein Structure, Tertiary, pubmed-meshheading:12960019-Rats, pubmed-meshheading:12960019-Receptors, Calcitriol, pubmed-meshheading:12960019-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:12960019-Receptors, Glucocorticoid, pubmed-meshheading:12960019-Receptors, Retinoic Acid, pubmed-meshheading:12960019-Receptors, Thyroid Hormone, pubmed-meshheading:12960019-Recombinant Fusion Proteins, pubmed-meshheading:12960019-Retinoid X Receptors, pubmed-meshheading:12960019-Transcription Factors, pubmed-meshheading:12960019-Transcriptional Activation, pubmed-meshheading:12960019-Vitamin D Response Element
pubmed:year
2003
pubmed:articleTitle
Two basic amino acids C-terminal of the proximal box specify functional binding of the vitamin D receptor to its rat osteocalcin deoxyribonucleic acid-responsive element.
pubmed:affiliation
Department of Biochemistry and Molecular Biophysics, College of Medicine, The University of Arizona, Tucson, Arizona 85724, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.