1ynw: Difference between revisions
New page: left|200px<br /> <applet load="1ynw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ynw, resolution 3.00Å" /> '''Crystal Structure o... |
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[[Image:1ynw.gif|left|200px]]<br /> | [[Image:1ynw.gif|left|200px]]<br /><applet load="1ynw" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1ynw, resolution 3.00Å" /> | caption="1ynw, resolution 3.00Å" /> | ||
'''Crystal Structure of Vitmain D Receptor and 9-cis Retinoic Acid Receptor DNA-Binding Domains Bound to a DR3 Response Element'''<br /> | '''Crystal Structure of Vitmain D Receptor and 9-cis Retinoic Acid Receptor DNA-Binding Domains Bound to a DR3 Response Element'''<br /> | ||
==Overview== | ==Overview== | ||
The Vitamin D receptor (VDR) is a ligand-responsive transcription factor | The Vitamin D receptor (VDR) is a ligand-responsive transcription factor that forms homo- or heterodimers on response elements composed of two hexameric half-sites separated by three base pairs of spacer DNA. Binding of 1alpha,25-dihydroxyvitamin D(3) to the full-length VDR causes destabilization of the VDR homodimer and formation of a heterodimeric complex with the 9-cis retinoic acid receptor (RXR). VDR and RXR DNA-binding domains (DBDs) do not mimic this behavior, however: VDR DBD homodimers are formed exclusively, even in the presence of excess RXR DBD. Exploiting the asymmetry of the heterodimer and our knowledge of the homodimeric DBD interface, we have engineered VDR mutants that disfavor the homodimeric complex and allow for the formation of heterodimeric DBD complexes with RXR on DR3 elements. One of these complexes has been crystallized and its structure determined. However, the polarity of the proteins relative to the DNA is non-physiological due to crystal packing between symmetry-related VDR DBD protomers. This reveals a flattened energy landscape that appears to rely on elements outside of the core DBD for response element discrimination in the heterodimer. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1YNW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 1YNW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YNW OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Gewirth, D | [[Category: Gewirth, D T.]] | ||
[[Category: Shaffer, P | [[Category: Shaffer, P L.]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
[[Category: vdr; rxr; nuclear receptor; protein-dna complex]] | [[Category: vdr; rxr; nuclear receptor; protein-dna complex]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:07:17 2008'' | ||
Revision as of 17:07, 21 February 2008
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Crystal Structure of Vitmain D Receptor and 9-cis Retinoic Acid Receptor DNA-Binding Domains Bound to a DR3 Response Element
OverviewOverview
The Vitamin D receptor (VDR) is a ligand-responsive transcription factor that forms homo- or heterodimers on response elements composed of two hexameric half-sites separated by three base pairs of spacer DNA. Binding of 1alpha,25-dihydroxyvitamin D(3) to the full-length VDR causes destabilization of the VDR homodimer and formation of a heterodimeric complex with the 9-cis retinoic acid receptor (RXR). VDR and RXR DNA-binding domains (DBDs) do not mimic this behavior, however: VDR DBD homodimers are formed exclusively, even in the presence of excess RXR DBD. Exploiting the asymmetry of the heterodimer and our knowledge of the homodimeric DBD interface, we have engineered VDR mutants that disfavor the homodimeric complex and allow for the formation of heterodimeric DBD complexes with RXR on DR3 elements. One of these complexes has been crystallized and its structure determined. However, the polarity of the proteins relative to the DNA is non-physiological due to crystal packing between symmetry-related VDR DBD protomers. This reveals a flattened energy landscape that appears to rely on elements outside of the core DBD for response element discrimination in the heterodimer.
DiseaseDisease
Known diseases associated with this structure: Osteoporosis, involutional, 166710 (1) OMIM:[601769], Rickets, vitamin D-resistant, type IIA OMIM:[601769]
About this StructureAbout this Structure
1YNW is a Protein complex structure of sequences from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Structural analysis of RXR-VDR interactions on DR3 DNA., Shaffer PL, Gewirth DT, J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):215-9. PMID:15225774
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