Linked Life Data

16690616

Source:http://linkedlifedata.com/resource/pubmed/id/16690616

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
28
pubmed:dateCreated
2006-7-10
pubmed:abstractText
Upon hormone binding, a hydrophobic coactivator binding groove is induced in the androgen receptor (AR) ligand-binding domain (LBD). This groove serves as high affinity docking site for alpha-helical FXXLF motifs present in the AR N-terminal domain and in AR cofactors. Study of the amino acid requirements at position +4 of the AR FXXLF motif revealed that most amino acid substitutions strongly reduced or completely abrogated AR LBD interaction. Strong interactions were still observed following substitution of Leu+4 by Phe or Met residues. Leu+4 to Met or Phe substitutions in the FXXLF motifs of AR cofactors ARA54 and ARA70 were also compatible with strong AR LBD binding. Like the corresponding FXXLF motifs, interactions of FXXFF and FXXMF variants of AR and ARA54 motifs were AR specific, whereas variants of the less AR-selective ARA70 motif displayed increased AR specificity. A survey of currently known AR-binding proteins revealed the presence of an FXXFF motif in gelsolin and an FXXMF motif in PAK6. In vivo fluorescence resonance energy transfer and functional protein-protein interaction assays showed direct, efficient, and specific interactions of both motifs with AR LBD. Mutation of these motifs abrogated interaction of gelsolin and PAK6 proteins with AR. In conclusion, we have demonstrated strong interaction of FXXFF and FXXMF motifs to the AR coactivator binding groove, thereby mediating specific binding of a subgroup of cofactors to the AR LBD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
19407-16
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16690616-Amino Acid Motifs, pubmed-meshheading:16690616-Amino Acid Sequence, pubmed-meshheading:16690616-Eye Proteins, pubmed-meshheading:16690616-Fluorescence Resonance Energy Transfer, pubmed-meshheading:16690616-Gelsolin, pubmed-meshheading:16690616-Homeodomain Proteins, pubmed-meshheading:16690616-Humans, pubmed-meshheading:16690616-Ligands, pubmed-meshheading:16690616-Molecular Sequence Data, pubmed-meshheading:16690616-Mutation, pubmed-meshheading:16690616-Paired Box Transcription Factors, pubmed-meshheading:16690616-Peptides, pubmed-meshheading:16690616-Protein Binding, pubmed-meshheading:16690616-Protein Structure, Tertiary, pubmed-meshheading:16690616-Receptors, Androgen, pubmed-meshheading:16690616-Repressor Proteins, pubmed-meshheading:16690616-Sequence Homology, Amino Acid
pubmed:year
2006
pubmed:articleTitle
Novel FXXFF and FXXMF motifs in androgen receptor cofactors mediate high affinity and specific interactions with the ligand-binding domain.
pubmed:affiliation
Department of Urology, Josephine Nefkens Institute, Erasmus MC, P. O. Box 1738, 3000 DR Rotterdam, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't