2c7a
From Proteopedia
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|PDB= 2c7a |SIZE=350|CAPTION= <scene name='initialview01'>2c7a</scene>, resolution 2.50Å | |PDB= 2c7a |SIZE=350|CAPTION= <scene name='initialview01'>2c7a</scene>, resolution 2.50Å | ||
|SITE= <scene name='pdbsite=AC1:Zn+Binding+Site+For+Chain+B'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Zn+Binding+Site+For+Chain+B'>AC1</scene> | ||
| - | |LIGAND= <scene name='pdbligand=ZN:ZINC ION'>ZN</scene> | + | |LIGAND= <scene name='pdbligand=DA:2'-DEOXYADENOSINE-5'-MONOPHOSPHATE'>DA</scene>, <scene name='pdbligand=DC:2'-DEOXYCYTIDINE-5'-MONOPHOSPHATE'>DC</scene>, <scene name='pdbligand=DG:2'-DEOXYGUANOSINE-5'-MONOPHOSPHATE'>DG</scene>, <scene name='pdbligand=DT:THYMIDINE-5'-MONOPHOSPHATE'>DT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2c7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c7a OCA], [http://www.ebi.ac.uk/pdbsum/2c7a PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2c7a RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
The DNA binding domain (DBD) of nuclear hormone receptors contains a highly conserved globular domain and a less conserved carboxyl-terminal extension (CTE). Despite previous observations that the CTEs of some classes of nuclear receptors are structured and interact with DNA outside of the hexanucleotide hormone response element (HRE), there has been no evidence for such a CTE among the steroid receptors. We have determined the structure of the progesterone receptor (PR)-DBD-CTE DNA complex at a resolution of 2.5 A, which revealed binding of the CTE to the minor groove flanking the HREs. Alanine substitutions of the interacting CTE residues reduced affinity for inverted repeat HREs separated by three nucleotides, and essentially abrogated binding to a single HRE. A highly compressed minor groove of the trinucleotide spacer and a novel dimerization interface were also observed. A PR binding site selection experiment revealed sequence preferences in the trinucleotide spacer and flanking DNA. These results, taken together, support the notion that sequences outside of the HREs influence the DNA binding affinity and specificity of steroid receptors. | The DNA binding domain (DBD) of nuclear hormone receptors contains a highly conserved globular domain and a less conserved carboxyl-terminal extension (CTE). Despite previous observations that the CTEs of some classes of nuclear receptors are structured and interact with DNA outside of the hexanucleotide hormone response element (HRE), there has been no evidence for such a CTE among the steroid receptors. We have determined the structure of the progesterone receptor (PR)-DBD-CTE DNA complex at a resolution of 2.5 A, which revealed binding of the CTE to the minor groove flanking the HREs. Alanine substitutions of the interacting CTE residues reduced affinity for inverted repeat HREs separated by three nucleotides, and essentially abrogated binding to a single HRE. A highly compressed minor groove of the trinucleotide spacer and a novel dimerization interface were also observed. A PR binding site selection experiment revealed sequence preferences in the trinucleotide spacer and flanking DNA. These results, taken together, support the notion that sequences outside of the HREs influence the DNA binding affinity and specificity of steroid receptors. | ||
| - | |||
| - | ==Disease== | ||
| - | Known disease associated with this structure: Progesterone resistance, 264080 (2) OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607311 607311]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Roemer, S C.]] | [[Category: Roemer, S C.]] | ||
[[Category: Sherman, L.]] | [[Category: Sherman, L.]] | ||
| - | [[Category: ZN]] | ||
[[Category: complex]] | [[Category: complex]] | ||
[[Category: dna-binding]] | [[Category: dna-binding]] | ||
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[[Category: zinc-finger]] | [[Category: zinc-finger]] | ||
| - | ''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 02:17:25 2008'' |
Revision as of 23:17, 30 March 2008
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| , resolution 2.50Å | |||||||
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| Sites: | |||||||
| Ligands: | , , , , | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
STRUCTURE OF THE PROGESTERONE RECEPTOR-DNA COMPLEX
Overview
The DNA binding domain (DBD) of nuclear hormone receptors contains a highly conserved globular domain and a less conserved carboxyl-terminal extension (CTE). Despite previous observations that the CTEs of some classes of nuclear receptors are structured and interact with DNA outside of the hexanucleotide hormone response element (HRE), there has been no evidence for such a CTE among the steroid receptors. We have determined the structure of the progesterone receptor (PR)-DBD-CTE DNA complex at a resolution of 2.5 A, which revealed binding of the CTE to the minor groove flanking the HREs. Alanine substitutions of the interacting CTE residues reduced affinity for inverted repeat HREs separated by three nucleotides, and essentially abrogated binding to a single HRE. A highly compressed minor groove of the trinucleotide spacer and a novel dimerization interface were also observed. A PR binding site selection experiment revealed sequence preferences in the trinucleotide spacer and flanking DNA. These results, taken together, support the notion that sequences outside of the HREs influence the DNA binding affinity and specificity of steroid receptors.
About this Structure
2C7A is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of the progesterone receptor-deoxyribonucleic acid complex: novel interactions required for binding to half-site response elements., Roemer SC, Donham DC, Sherman L, Pon VH, Edwards DP, Churchill ME, Mol Endocrinol. 2006 Dec;20(12):3042-52. Epub 2006 Aug 24. PMID:16931575
Page seeded by OCA on Mon Mar 31 02:17:25 2008
Categories: Homo sapiens | Single protein | Churchill, M E.A. | Donham, D C. | Edwards, D P. | Pon, V H. | Roemer, S C. | Sherman, L. | Complex | Dna-binding | Metal-binding | Nuclear protein | Phosphorylation | Progesterone receptor | Receptor/dna complex | Steroid-binding | Transcription regulation | Zinc | Zinc-finger
