1zdt
From Proteopedia
(Difference between revisions)
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<StructureSection load='1zdt' size='340' side='right'caption='[[1zdt]], [[Resolution|resolution]] 2.10Å' scene=''> | <StructureSection load='1zdt' size='340' side='right'caption='[[1zdt]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[1zdt]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/ | + | <table><tr><td colspan='2'>[[1zdt]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZDT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZDT FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PEF:DI-PALMITOYL-3-SN-PHOSPHATIDYLETHANOLAMINE'>PEF</scene></td></tr> |
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1zdt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zdt OCA], [https://pdbe.org/1zdt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zdt RCSB], [https://www.ebi.ac.uk/pdbsum/1zdt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zdt ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1zdt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zdt OCA], [https://pdbe.org/1zdt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zdt RCSB], [https://www.ebi.ac.uk/pdbsum/1zdt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zdt ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
| - | + | [https://www.uniprot.org/uniprot/STF1_HUMAN STF1_HUMAN] Defects in NR5A1 are a cause of 46,XY sex reversal type 3 (SRXY3) [MIM:[https://omim.org/entry/612965 612965]. A condition characterized by male-to-female sex reversal in the presence of a normal 46,XY karyotype.<ref>PMID:10369247</ref> <ref>PMID:11932325</ref> <ref>PMID:17200175</ref> <ref>PMID:17694559</ref> Defects in NR5A1 are a cause of adrenocortical insufficiency without ovarian defect (ACIWOD) [MIM:[https://omim.org/entry/184757 184757]. ACIWOD is characterized by severe 'slackness' muscular hypotonia. There is decreased sodium, increased potassium and elevated ACTH.<ref>PMID:11038323</ref> Defects in NR5A1 are the cause of premature ovarian failure type 7 (POF7) [MIM:[https://omim.org/entry/612964 612964]. An ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol.<ref>PMID:19246354</ref> Defects in NR5A1 are the cause of spermatogenic failure type 8 (SPGF8) [MIM:[https://omim.org/entry/613957 613957]. SPGF8 is an infertility disorder characterized by spermatogenesis failure and severe oligozoospermia.<ref>PMID:20887963</ref> | |
== Function == | == Function == | ||
| - | + | [https://www.uniprot.org/uniprot/STF1_HUMAN STF1_HUMAN] Transcriptional activator. Seems to be essential for sexual differentiation and formation of the primary steroidogenic tissues. Binds to the Ad4 site found in the promoter region of steroidogenic P450 genes such as CYP11A, CYP11B and CYP21B. Also regulates the AMH/Muellerian inhibiting substance gene as well as the AHCH and STAR genes. 5'-YCAAGGYC-3' and 5'-RRAGGTCA-3' are the consensus sequences for the recognition by NR5A1. The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional avtivity. Binds phosphatidylcholine (By similarity). Binds phospholipids with a phosphatidylinositol (PI) headgroup, in particular PI(3,4)P2 and PI(3,4,5)P3. Activated by the phosphorylation of NR5A1 by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation.<ref>PMID:17210646</ref> | |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1zdt ConSurf]. | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1zdt ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Steroidogenic factor-1 (SF-1) and liver receptor homologue-1 (LRH-1) belong to the fushi tarazu factor 1 subfamily of nuclear receptors. SF-1 is an essential factor for sex determination during development and regulates adrenal and gonadal steroidogenesis in the adult, whereas LRH-1 is a critical factor for development of endodermal tissues and regulates cholesterol and bile acid homeostasis. Regulatory ligands are unknown for SF-1 and LRH-1. A reported mouse LRH-1 structure revealed an empty pocket in a region commonly occupied by ligands in the structures of other nuclear receptors, and pocket-filling mutations did not alter the constitutive activity observed. Here we report the crystal structures of the putative ligand-binding domains of human SF-1 at 2.1-A resolution and human LRH-1 at 2.5-A resolution. Both structures bind a coactivator-derived peptide at the canonical activation-function surface, thus adopting the transcriptionally activating conformation. In human LRH-1, coactivator peptide binding also occurs to a second site. We discovered in both structures a phospholipid molecule bound in a pocket of the putative ligand-binding domain. MS analysis of the protein samples used for crystallization indicated that the two proteins associate with a range of phospholipids. Mutations of the pocket-lining residues reduced the transcriptional activities of SF-1 and LRH-1 in mammalian cell transfection assays without affecting their expression levels. These results suggest that human SF-1 and LRH-1 may be ligand-binding receptors, although it remains to be seen if phospholipids or possibly other molecules regulate SF-1 or LRH-1 under physiological conditions. | ||
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| - | The crystal structures of human steroidogenic factor-1 and liver receptor homologue-1.,Wang W, Zhang C, Marimuthu A, Krupka HI, Tabrizizad M, Shelloe R, Mehra U, Eng K, Nguyen H, Settachatgul C, Powell B, Milburn MV, West BL Proc Natl Acad Sci U S A. 2005 May 24;102(21):7505-10. Epub 2005 May 16. PMID:15897460<ref>PMID:15897460</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 1zdt" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Eng | + | [[Category: Eng K]] |
| - | [[Category: Krupka | + | [[Category: Krupka HI]] |
| - | [[Category: Marimuthu | + | [[Category: Marimuthu A]] |
| - | [[Category: Mehra | + | [[Category: Mehra U]] |
| - | [[Category: Milburn | + | [[Category: Milburn MV]] |
| - | [[Category: Nguyen | + | [[Category: Nguyen H]] |
| - | [[Category: Powell | + | [[Category: Powell B]] |
| - | [[Category: Settachatgul | + | [[Category: Settachatgul C]] |
| - | [[Category: Shelloe | + | [[Category: Shelloe R]] |
| - | [[Category: Tabrizizad | + | [[Category: Tabrizizad M]] |
| - | [[Category: Wang | + | [[Category: Wang W]] |
| - | [[Category: West | + | [[Category: West BL]] |
| - | [[Category: Zhang | + | [[Category: Zhang C]] |
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Current revision
The Crystal Structure of Human Steroidogenic Factor-1
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Categories: Homo sapiens | Large Structures | Eng K | Krupka HI | Marimuthu A | Mehra U | Milburn MV | Nguyen H | Powell B | Settachatgul C | Shelloe R | Tabrizizad M | Wang W | West BL | Zhang C
