1xq3: Difference between revisions
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= Ar, Nr3c4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= Ar, Nr3c4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1i37|1I37]], [[1e3g|1E3G]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1xq3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xq3 OCA], [http://www.ebi.ac.uk/pdbsum/1xq3 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1xq3 RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
The androgen receptor (AR) is required for male sex development and contributes to prostate cancer cell survival. In contrast to other nuclear receptors that bind the LXXLL motifs of coactivators, the AR ligand binding domain is preferentially engaged in an interdomain interaction with the AR FXXLF motif. Reported here are crystal structures of the ligand-activated AR ligand binding domain with and without bound FXXLF and LXXLL peptides. Key residues that establish motif binding specificity are identified through comparative structure-function and mutagenesis studies. A mechanism in prostate cancer is suggested by a functional AR mutation at a specificity-determining residue that recovers coactivator LXXLL motif binding. An activation function transition hypothesis is proposed in which an evolutionary decline in LXXLL motif binding parallels expansion and functional dominance of the NH(2)-terminal transactivation domain in the steroid receptor subfamily. | The androgen receptor (AR) is required for male sex development and contributes to prostate cancer cell survival. In contrast to other nuclear receptors that bind the LXXLL motifs of coactivators, the AR ligand binding domain is preferentially engaged in an interdomain interaction with the AR FXXLF motif. Reported here are crystal structures of the ligand-activated AR ligand binding domain with and without bound FXXLF and LXXLL peptides. Key residues that establish motif binding specificity are identified through comparative structure-function and mutagenesis studies. A mechanism in prostate cancer is suggested by a functional AR mutation at a specificity-determining residue that recovers coactivator LXXLL motif binding. An activation function transition hypothesis is proposed in which an evolutionary decline in LXXLL motif binding parallels expansion and functional dominance of the NH(2)-terminal transactivation domain in the steroid receptor subfamily. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Stewart, E L.]] | [[Category: Stewart, E L.]] | ||
[[Category: Wilson, E M.]] | [[Category: Wilson, E M.]] | ||
[[Category: | [[Category: crystal structure]] | ||
[[Category: | [[Category: human androgen receptor ligand binding domain]] | ||
[[Category: r1881]] | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:53:06 2008'' | ||
Revision as of 00:53, 31 March 2008
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| , resolution 2.25Å | |||||||
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| Ligands: | |||||||
| Gene: | Ar, Nr3c4 (Homo sapiens) | ||||||
| Related: | 1I37, 1E3G
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of the human androgen receptor ligand binding domain bound with R1881
OverviewOverview
The androgen receptor (AR) is required for male sex development and contributes to prostate cancer cell survival. In contrast to other nuclear receptors that bind the LXXLL motifs of coactivators, the AR ligand binding domain is preferentially engaged in an interdomain interaction with the AR FXXLF motif. Reported here are crystal structures of the ligand-activated AR ligand binding domain with and without bound FXXLF and LXXLL peptides. Key residues that establish motif binding specificity are identified through comparative structure-function and mutagenesis studies. A mechanism in prostate cancer is suggested by a functional AR mutation at a specificity-determining residue that recovers coactivator LXXLL motif binding. An activation function transition hypothesis is proposed in which an evolutionary decline in LXXLL motif binding parallels expansion and functional dominance of the NH(2)-terminal transactivation domain in the steroid receptor subfamily.
About this StructureAbout this Structure
1XQ3 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for androgen receptor interdomain and coactivator interactions suggests a transition in nuclear receptor activation function dominance., He B, Gampe RT Jr, Kole AJ, Hnat AT, Stanley TB, An G, Stewart EL, Kalman RI, Minges JT, Wilson EM, Mol Cell. 2004 Nov 5;16(3):425-38. PMID:15525515
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