1zgy

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(Difference between revisions)

Revision as of 08:21, 12 October 2017

Structural and Biochemical Basis for Selective Repression of the Orphan Nuclear Receptor LRH-1 by SHP

Structural highlights

1zgy is a 2 chain structure with sequence from Buffalo rat and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PPAT_HUMAN] Dephosphorylates receptor tyrosine-protein kinase erbB-4 and inhibits the ligand-induced proteolytic cleavage.^[1] [NR0B2_RAT] Acts as a transcriptional regulator. Acts as a negative regulator of receptor-dependent signaling pathways. Specifically inhibits transactivation of the nuclear receptor with whom it interacts. Inhibits transcriptional activity of NEUROD1 on E-box-containing promoter by interfering with the coactivation function of the p300/CBP-mediated trancription complex for NEUROD1.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The functional interaction between the orphan nuclear receptors small heterodimer partner (SHP) and liver receptor homolog 1 (LRH-1), where SHP binds to LRH-1 and represses its constitutive transcriptional activity, is crucial for regulating genes involved in cholesterol homeostasis. Here, we report structural and biochemical analyses of the LRH-1/SHP interaction. The crystal structure and modeling studies of the LRH-1 ligand-binding domain bound to either of the two LXXLL-related motifs of SHP show that the receptor undergoes conformational changes to accommodate the SHP docking and reveal key residues that determine the potency and selectivity of SHP binding. Through a combination of mutagenesis and binding studies, we demonstrate that only the second SHP LXXLL motif is required for repressing LRH-1, and this motif displays a strong preference for binding to LRH-1 over the closely related receptor steroidogeneic factor 1 (SF-1). Structural comparisons indicate that this binding selectivity is determined by residues flanking the core LXXLL motifs. These results establish a structural model for understanding how SHP interacts with LRH-1 to regulate cholesterol homeostasis and provide new insights into how nuclear receptor/coregulator selectivity is achieved.

Structural and biochemical basis for selective repression of the orphan nuclear receptor liver receptor homolog 1 by small heterodimer partner.,Li Y, Choi M, Suino K, Kovach A, Daugherty J, Kliewer SA, Xu HE Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9505-10. Epub 2005 Jun 23. PMID:15976031^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Fleisig H, El-Din El-Husseini A, Vincent SR. Regulation of ErbB4 phosphorylation and cleavage by a novel histidine acid phosphatase. Neuroscience. 2004;127(1):91-100. PMID:15219672 doi:10.1016/j.neuroscience.2004.04.060
↑ Li Y, Choi M, Suino K, Kovach A, Daugherty J, Kliewer SA, Xu HE. Structural and biochemical basis for selective repression of the orphan nuclear receptor liver receptor homolog 1 by small heterodimer partner. Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9505-10. Epub 2005 Jun 23. PMID:15976031

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1zgy"

@@ Line 1: / Line 1: @@
 ==Structural and Biochemical Basis for Selective Repression of the Orphan Nuclear Receptor LRH-1 by SHP==
 <StructureSection load='1zgy' size='340' side='right' caption='[[1zgy]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1zgy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZGY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ZGY FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1zgy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZGY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ZGY FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BRL:2,4-THIAZOLIDIINEDIONE,+5-[[4-[2-(METHYL-2-PYRIDINYLAMINO)ETHOXY]PHENYL]METHYL]-(9CL)'>BRL</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1zgy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zgy OCA], [http://pdbe.org/1zgy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1zgy RCSB], [http://www.ebi.ac.uk/pdbsum/1zgy PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1zgy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zgy OCA], [http://pdbe.org/1zgy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1zgy RCSB], [http://www.ebi.ac.uk/pdbsum/1zgy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1zgy ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 17: @@
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</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/chain_selection.php?pdb_ID=2ata 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=1zgy ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 27: / Line 28: @@
 </div>
 <div class="pdbe-citations 1zgy" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Peroxisome Proliferator-Activated Receptors|Peroxisome Proliferator-Activated Receptors]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Buffalo rat]]
-[[Category: Rattus norvegicus]]
+[[Category: Human]]
 [[Category: Choi, M]]
 [[Category: Daugherty, J]]

1zgy

From Proteopedia

Revision as of 08:21, 12 October 2017

Structural and Biochemical Basis for Selective Repression of the Orphan Nuclear Receptor LRH-1 by SHP

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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