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2a66
From Proteopedia
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| - | [[Image:2a66.gif|left|200px]] | + | [[Image:2a66.gif|left|200px]] |
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| - | '''Human Liver Receptor Homologue DNA-Binding Domain (hLRH-1 DBD) in Complex with dsDNA from the hCYP7A1 Promoter''' | + | {{Structure |
| + | |PDB= 2a66 |SIZE=350|CAPTION= <scene name='initialview01'>2a66</scene>, resolution 2.20Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <scene name='pdbligand=ACT:ACETATE ION'>ACT</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= NR5A2, B1F, CPF, FTF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Human Liver Receptor Homologue DNA-Binding Domain (hLRH-1 DBD) in Complex with dsDNA from the hCYP7A1 Promoter''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2A66 is a [ | + | 2A66 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A66 OCA]. |
==Reference== | ==Reference== | ||
| - | Crystal structure of the human LRH-1 DBD-DNA complex reveals Ftz-F1 domain positioning is required for receptor activity., Solomon IH, Hager JM, Safi R, McDonnell DP, Redinbo MR, Ortlund EA, J Mol Biol. 2005 Dec 16;354(5):1091-102. Epub 2005 Oct 27. PMID:[http:// | + | Crystal structure of the human LRH-1 DBD-DNA complex reveals Ftz-F1 domain positioning is required for receptor activity., Solomon IH, Hager JM, Safi R, McDonnell DP, Redinbo MR, Ortlund EA, J Mol Biol. 2005 Dec 16;354(5):1091-102. Epub 2005 Oct 27. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16289203 16289203] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: zinc finger]] | [[Category: zinc finger]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:45:51 2008'' |
Revision as of 13:45, 20 March 2008
| |||||||
| , resolution 2.20Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | NR5A2, B1F, CPF, FTF (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human Liver Receptor Homologue DNA-Binding Domain (hLRH-1 DBD) in Complex with dsDNA from the hCYP7A1 Promoter
Overview
The DNA-binding and ligand-binding functions of nuclear receptors are localized to independent domains separated by a flexible hinge. The DNA-binding domain (DBD) of the human liver receptor homologue-1 (hLRH-1), which controls genes central to development and metabolic homeostasis, interacts with monomeric DNA response elements and contains an Ftz-F1 motif that is unique to the NR5A nuclear receptor subfamily. Here, we present the 2.2A resolution crystal structure of the hLRH-1 DBD in complex with duplex DNA, and elucidate the sequence-specific DNA contacts essential for the ability of LRH-1 to bind to DNA as a monomer. We show that the unique Ftz-F1 domain folds into a novel helix that packs against the DBD but does not contact DNA. Mutations expected to disrupt the positioning of the Ftz-F1 helix do not eliminate DNA binding but reduce the transcriptional activity of full-length LRH-1 significantly. Moreover, we find that altering the Ftz-F1 helix positioning eliminates the enhancement of LRH-1-mediated transcription by the coactivator GRIP1, an action that is associated primarily with the distantly located ligand-binding domain (LBD). Taken together, these results indicate that subtle structural changes in a nuclear receptor DBD can exert long-range functional effects on the LBD of a receptor, and significantly impact transcriptional regulation.
About this Structure
2A66 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of the human LRH-1 DBD-DNA complex reveals Ftz-F1 domain positioning is required for receptor activity., Solomon IH, Hager JM, Safi R, McDonnell DP, Redinbo MR, Ortlund EA, J Mol Biol. 2005 Dec 16;354(5):1091-102. Epub 2005 Oct 27. PMID:16289203
Page seeded by OCA on Thu Mar 20 15:45:51 2008
