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| {{STRUCTURE_2a66| PDB=2a66 | SCENE= }} | | {{STRUCTURE_2a66| PDB=2a66 | SCENE= }} |
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| '''Human Liver Receptor Homologue DNA-Binding Domain (hLRH-1 DBD) in Complex with dsDNA from the hCYP7A1 Promoter'''
| | ===Human Liver Receptor Homologue DNA-Binding Domain (hLRH-1 DBD) in Complex with dsDNA from the hCYP7A1 Promoter=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_16289203}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 16289203 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_16289203}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Transcription factor]] | | [[Category: Transcription factor]] |
| [[Category: Zinc finger]] | | [[Category: Zinc finger]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 18:39:28 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 06:26:42 2008'' |
