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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2005-2-21
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pubmed:databankReference |
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pubmed:abstractText |
The orphan nuclear receptor steroidogenic factor 1 (SF-1) regulates the differentiation and function of endocrine glands. Although SF-1 is constitutively active in cell-based assays, it is not known whether this transcriptional activity is modulated by ligands. Here, we describe the 1.5 angstroms crystal structure of the SF-1 ligand binding domain in complex with an LXXLL motif from a coregulator protein. The structure reveals the presence of a phospholipid ligand in a surprisingly large pocket (approximately 1600 angstroms3), with the receptor adopting the canonical active conformation. The bound phospholipid is readily exchanged and modulates SF-1 interactions with coactivators. Mutations designed to reduce the size of the SF-1 pocket or to disrupt hydrogen bonds with the phospholipid abolish SF-1/coactivator interactions and significantly reduce SF-1 transcriptional activity. These findings provide evidence that SF-1 is regulated by endogenous ligands and suggest an unexpected relationship between phospholipids and endocrine development and function.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Acetyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Ncoa1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Coactivator 1,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipids,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Steroidogenic Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/steroidogenic factor 1, mouse
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1097-2765
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
18
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
491-502
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15721253-Amino Acid Sequence,
pubmed-meshheading:15721253-Animals,
pubmed-meshheading:15721253-Binding Sites,
pubmed-meshheading:15721253-Crystallography,
pubmed-meshheading:15721253-DNA-Binding Proteins,
pubmed-meshheading:15721253-Histone Acetyltransferases,
pubmed-meshheading:15721253-Homeodomain Proteins,
pubmed-meshheading:15721253-Hydrogen Bonding,
pubmed-meshheading:15721253-Ligands,
pubmed-meshheading:15721253-Mice,
pubmed-meshheading:15721253-Molecular Sequence Data,
pubmed-meshheading:15721253-Mutation,
pubmed-meshheading:15721253-Nuclear Receptor Coactivator 1,
pubmed-meshheading:15721253-Phospholipids,
pubmed-meshheading:15721253-Protein Conformation,
pubmed-meshheading:15721253-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:15721253-Sequence Homology, Amino Acid,
pubmed-meshheading:15721253-Steroidogenic Factor 1,
pubmed-meshheading:15721253-Transcription, Genetic,
pubmed-meshheading:15721253-Transcription Factors
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pubmed:year |
2005
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pubmed:articleTitle |
Crystallographic identification and functional characterization of phospholipids as ligands for the orphan nuclear receptor steroidogenic factor-1.
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pubmed:affiliation |
Laboratory of Structural Sciences, Van Andel Research Institute, 333 Bostwick Avenue, Grand Rapids, MI 49503, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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