Linked Life Data

7727406

Source:http://linkedlifedata.com/resource/pubmed/id/7727406

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
1995-6-1
pubmed:abstractText
The ligand-dependent transactivating properties of retinoic acid receptors are controlled through a complex structure at the C-terminus of these proteins, commonly referred to as the hormone binding domain. This domain is involved not only in ligand recognition but also in protein-protein interactions such as homo- and heterodimerization processes. To identify more precisely regions of the human all-trans-retinoic acid receptor alpha (hRAR alpha) that are involved in ligand binding, we constructed a series of deletion mutants of this molecule and overexpressed them in bacteria. We found that the C-terminal part of the D domain (amino acids 186-198) was necessary for ligand binding. The F domain and the 10 C-terminal amino acids of the E domain were dispensable for high-affinity binding of various natural and synthetic retinoids. A further deletion to position 403 resulted in a moderate decrease in affinity for all-trans-(ATRA) and 9-cis-retinoic acids, whereas the binding of two RAR alpha-specific ligands (Am80 and Am580) was abolished. In addition, hRAR alpha and the minimal hormone binding domain (amino acids 186-410) bound ATRA with a positive, cooperative mechanism. This behavior was not observed with CD367, a conformationally restricted synthetic retinoid. The positive cooperativity could be correlated with stable ATRA binding to RAR homodimers, whose formation was triggered by ligand. In the same conditions, only monomeric CD367-RAR alpha complexes were detected. These data indicate that ligand binding to hRAR alpha requires the presence of part of the D domain, whereas the C-terminal end of the E domain is involved in more subtle ligand recognition processes.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5477-85
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:7727406-Amino Acid Sequence, pubmed-meshheading:7727406-Animals, pubmed-meshheading:7727406-Binding Sites, pubmed-meshheading:7727406-Cloning, Molecular, pubmed-meshheading:7727406-Conserved Sequence, pubmed-meshheading:7727406-Drosophila, pubmed-meshheading:7727406-Genetic Vectors, pubmed-meshheading:7727406-Humans, pubmed-meshheading:7727406-Kinetics, pubmed-meshheading:7727406-Ligands, pubmed-meshheading:7727406-Macromolecular Substances, pubmed-meshheading:7727406-Molecular Sequence Data, pubmed-meshheading:7727406-Polymerase Chain Reaction, pubmed-meshheading:7727406-Receptors, Retinoic Acid, pubmed-meshheading:7727406-Recombinant Proteins, pubmed-meshheading:7727406-Restriction Mapping, pubmed-meshheading:7727406-Sequence Deletion, pubmed-meshheading:7727406-Sequence Homology, Amino Acid, pubmed-meshheading:7727406-Substrate Specificity, pubmed-meshheading:7727406-Tretinoin
pubmed:year
1995
pubmed:articleTitle
Structural determinants of the ligand-binding site of the human retinoic acid receptor alpha.
pubmed:affiliation
CJF-INSERM 92-03, Laboratoire de Biochimie Structurale, Faculté de Médecine de Lille, France.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't