1kb6: Difference between revisions
New page: left|200px<br /> <applet load="1kb6" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kb6, resolution 2.70Å" /> '''Crystal Structure o... |
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[[Image:1kb6.gif|left|200px]]<br /> | [[Image:1kb6.gif|left|200px]]<br /><applet load="1kb6" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1kb6, resolution 2.70Å" /> | caption="1kb6, resolution 2.70Å" /> | ||
'''Crystal Structure of VDR DNA-binding Domain Bound to Rat Osteocalcin (OC) Response Element'''<br /> | '''Crystal Structure of VDR DNA-binding Domain Bound to Rat Osteocalcin (OC) Response Element'''<br /> | ||
==Overview== | ==Overview== | ||
The vitamin D receptor (VDR) forms homo- or heterodimers on response | The vitamin D receptor (VDR) forms homo- or heterodimers on response elements composed of two hexameric half-sites separated by 3 bp of spacer DNA. We describe here the crystal structures at 2.7-2.8 A resolution of the VDR DNA-binding region (DBD) in complex with response elements from three different promoters: osteopontin (SPP), canonical DR3 and osteocalcin (OC). These structures reveal the chemical basis for the increased affinity of VDR for the SPP response element, and for the poor stability of the VDR-OC complex, relative to the canonical DR3 response element. The homodimeric protein-protein interface is stabilized by van der Waals interactions and is predominantly non-polar. An extensive alpha-helix at the C-terminal end of the VDR DBD resembles that found in the thyroid hormone receptor (TR), and suggests a mechanism by which VDR and TR discriminate among response elements. Selective structure-based mutations in the asymmetric homodimeric interface result in a VDR DBD protein that is defective in homodimerization but now forms heterodimers with the 9-cis retinoic acid receptor (RXR) DBD. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1KB6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence 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:// | 1KB6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence 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=1KB6 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Gewirth, D | [[Category: Gewirth, D T.]] | ||
[[Category: Shaffer, P | [[Category: Shaffer, P L.]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
[[Category: nuclear receptor]] | [[Category: nuclear receptor]] | ||
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[[Category: vitamin d]] | [[Category: vitamin d]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:32:06 2008'' | ||
Revision as of 14:32, 21 February 2008
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Crystal Structure of VDR DNA-binding Domain Bound to Rat Osteocalcin (OC) Response Element
OverviewOverview
The vitamin D receptor (VDR) forms homo- or heterodimers on response elements composed of two hexameric half-sites separated by 3 bp of spacer DNA. We describe here the crystal structures at 2.7-2.8 A resolution of the VDR DNA-binding region (DBD) in complex with response elements from three different promoters: osteopontin (SPP), canonical DR3 and osteocalcin (OC). These structures reveal the chemical basis for the increased affinity of VDR for the SPP response element, and for the poor stability of the VDR-OC complex, relative to the canonical DR3 response element. The homodimeric protein-protein interface is stabilized by van der Waals interactions and is predominantly non-polar. An extensive alpha-helix at the C-terminal end of the VDR DBD resembles that found in the thyroid hormone receptor (TR), and suggests a mechanism by which VDR and TR discriminate among response elements. Selective structure-based mutations in the asymmetric homodimeric interface result in a VDR DBD protein that is defective in homodimerization but now forms heterodimers with the 9-cis retinoic acid receptor (RXR) DBD.
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
1KB6 is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis of VDR-DNA interactions on direct repeat response elements., Shaffer PL, Gewirth DT, EMBO J. 2002 May 1;21(9):2242-52. PMID:11980721
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