2a66: Difference between revisions

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Revision as of 01:48, 31 March 2008

File:2a66.gif

, resolution 2.20Å

Ligands:

, , , , ,

Gene:

NR5A2, B1F, CPF, FTF (Homo sapiens)

Resources:

FirstGlance, OCA, PDBsum, RCSB

Coordinates:

save as pdb, mmCIF, xml

Human Liver Receptor Homologue DNA-Binding Domain (hLRH-1 DBD) in Complex with dsDNA from the hCYP7A1 Promoter

OverviewOverview

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 StructureAbout this Structure

2A66 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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 Mon Mar 31 01:48:20 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 4: / Line 4: @@
 |PDB= 2a66 |SIZE=350|CAPTION= <scene name='initialview01'>2a66</scene>, resolution 2.20&Aring;
 |SITE=
-|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <scene name='pdbligand=ACT:ACETATE ION'>ACT</scene>
+|LIGAND= <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=DA:2&#39;-DEOXYADENOSINE-5&#39;-MONOPHOSPHATE'>DA</scene>, <scene name='pdbligand=DC:2&#39;-DEOXYCYTIDINE-5&#39;-MONOPHOSPHATE'>DC</scene>, <scene name='pdbligand=DG:2&#39;-DEOXYGUANOSINE-5&#39;-MONOPHOSPHATE'>DG</scene>, <scene name='pdbligand=DT:THYMIDINE-5&#39;-MONOPHOSPHATE'>DT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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])
+|DOMAIN=
+|RELATEDENTRY=
+|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2a66 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a66 OCA], [http://www.ebi.ac.uk/pdbsum/2a66 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2a66 RCSB]</span>
 }}
@@ Line 28: / Line 31: @@
 [[Category: Safi, R.]]
 [[Category: Solomon, I H.]]
-[[Category: ACT]]
-[[Category: ZN]]
 [[Category: c-terminal extension]]
 [[Category: dna-binding domain]]
@@ Line 38: / Line 39: @@
 [[Category: zinc finger]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:45:51 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:48:20 2008''