Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
|
| pubmed:dateCreated |
1991-10-29
|
| pubmed:abstractText |
By analogy with steroid receptors, human placental thyroid hormone nuclear receptor (hTR beta 1) could be divided into four functional domains: A/B (Met1-Leu101), C (Cys102-Ala170), D (Thr171-Lys237), and E (Arg238-Asp456). The E domain was thought to bind thyroid hormone. To evaluate whether domain E alone is sufficient to bind T3 or requires the presence of other domains for functional T3-binding activity, a series of deletion mutants was constructed. The mutants were expressed in Escherichia coli, and the expressed proteins were purified. Analysis of the T3-binding affinity and analog specificity of the purified truncated hTR beta 1 indicated that domain E alone did not have T3-binding activity. Extension of the amino-terminal sequence of domain E to include part of domain D yielded a mutant (Lys201-Asp456) with a Ka for T3 of 0.5 +/- 0.2 x 10(9) M-1. Further extension to include the entire domain D (Met169-Asp456) yielded a mutant with T3-binding activity with a Ka of 0.8 +/- 0.1 x 10(9) M-1. Further extension of the amino-terminal sequence to include domain C increased the affinity for T3 by nearly 2-fold (Ka = 1.5 +/- 0.4 x 10(9) M-1). The Ka for the wild-type hTR beta 1 is 1.5 +/- 0.2 x 10(9) M-1. Furthermore, mutant (Met169-Asp456) binds to 3',5',3-triiodo-L-thyropropionic acid, D-T3, L-T4, and L-T3 with 307%, 37%, 7%, and 0.1%, respectively, of the activity of L-T3. This order of analog affinity is similar to that of the wild-type hTR beta 1.(ABSTRACT TRUNCATED AT 250 WORDS)
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
0888-8809
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
5
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
485-92
|
| pubmed:dateRevised |
2006-5-1
|
| pubmed:meshHeading |
pubmed-meshheading:1922081-Base Sequence,
pubmed-meshheading:1922081-Binding, Competitive,
pubmed-meshheading:1922081-Blotting, Northern,
pubmed-meshheading:1922081-Blotting, Western,
pubmed-meshheading:1922081-Chromosome Deletion,
pubmed-meshheading:1922081-Dose-Response Relationship, Drug,
pubmed-meshheading:1922081-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:1922081-Escherichia coli,
pubmed-meshheading:1922081-Humans,
pubmed-meshheading:1922081-Molecular Sequence Data,
pubmed-meshheading:1922081-Plasmids,
pubmed-meshheading:1922081-Protein Biosynthesis,
pubmed-meshheading:1922081-RNA, Messenger,
pubmed-meshheading:1922081-Receptors, Thyroid Hormone,
pubmed-meshheading:1922081-Transfection,
pubmed-meshheading:1922081-Triiodothyronine
|
| pubmed:year |
1991
|
| pubmed:articleTitle |
An essential role of domain D in the hormone-binding activity of human beta 1 thyroid hormone nuclear receptor.
|
| pubmed:affiliation |
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
|
| pubmed:publicationType |
Journal Article
|