5sy5

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Revision as of 11:14, 16 September 2020

Crystal Structure of the Heterodimeric NPAS1-ARNT Complex

Structural highlights

5sy5 is a 6 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	Arnt (LK3 transgenic mice), Npas1 (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ARNT_MOUSE] Required for activity of the Ah (dioxin) receptor. This protein is required for the ligand-binding subunit to translocate from the cytosol to the nucleus after ligand binding. The complex then initiates transcription of genes involved in the activation of PAH procarcinogens. The heterodimer with HIF1A or EPAS1/HIF2A functions as a transcriptional regulator of the adaptive response to hypoxia (By similarity). [NPAS1_MOUSE] May control regulatory pathways relevant to schizophrenia and to psychotic illness. May play a role in late central nervous system development by modulating EPO expression in response to cellular oxygen level.^[1] ^[2]

Publication Abstract from PubMed

The neuronal PAS domain proteins NPAS1 and NPAS3 are members of the basic helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) family, and their genetic deficiencies are linked to a variety of human psychiatric disorders including schizophrenia, autism spectrum disorders and bipolar disease. NPAS1 and NPAS3 must each heterodimerize with the aryl hydrocarbon receptor nuclear translocator (ARNT), to form functional transcription complexes capable of DNA binding and gene regulation. Here we examined the crystal structures of multi-domain NPAS1-ARNT and NPAS3-ARNT-DNA complexes, discovering each to contain four putative ligand-binding pockets. Through expanded architectural comparisons between these complexes and HIF-1alpha-ARNT, HIF-2alpha-ARNT and CLOCK-BMAL1, we show the wider mammalian bHLH-PAS family is capable of multi-ligand-binding and presents as an ideal class of transcription factors for direct targeting by small-molecule drugs.

NPAS1-ARNT and NPAS3-ARNT crystal structures implicate the bHLH-PAS family as multi-ligand binding transcription factors.,Wu D, Su X, Potluri N, Kim Y, Rastinejad F Elife. 2016 Oct 26;5. pii: e18790. doi: 10.7554/eLife.18790. PMID:27782878^[3]

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

References

↑ Erbel-Sieler C, Dudley C, Zhou Y, Wu X, Estill SJ, Han T, Diaz-Arrastia R, Brunskill EW, Potter SS, McKnight SL. Behavioral and regulatory abnormalities in mice deficient in the NPAS1 and NPAS3 transcription factors. Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13648-53. Epub 2004 Sep 3. PMID:15347806 doi:http://dx.doi.org/10.1073/pnas.0405310101
↑ Ohsawa S, Hamada S, Kakinuma Y, Yagi T, Miura M. Novel function of neuronal PAS domain protein 1 in erythropoietin expression in neuronal cells. J Neurosci Res. 2005 Feb 15;79(4):451-8. PMID:15635607 doi:http://dx.doi.org/10.1002/jnr.20365
↑ Wu D, Su X, Potluri N, Kim Y, Rastinejad F. NPAS1-ARNT and NPAS3-ARNT crystal structures implicate the bHLH-PAS family as multi-ligand binding transcription factors. Elife. 2016 Oct 26;5. pii: e18790. doi: 10.7554/eLife.18790. PMID:27782878 doi:http://dx.doi.org/10.7554/eLife.18790

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5sy5"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of the Heterodimeric NPAS1-ARNT Complex==
-<StructureSection load='5sy5' size='340' side='right' caption='[[5sy5]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
+<StructureSection load='5sy5' size='340' side='right'caption='[[5sy5]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5sy5]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SY5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5SY5 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5sy5]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SY5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5SY5 FirstGlance]. <br>
-</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=5sy5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sy5 OCA], [http://pdbe.org/5sy5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5sy5 RCSB], [http://www.ebi.ac.uk/pdbsum/5sy5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5sy5 ProSAT]</span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Arnt ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Npas1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5sy5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sy5 OCA], [http://pdbe.org/5sy5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5sy5 RCSB], [http://www.ebi.ac.uk/pdbsum/5sy5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5sy5 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 21: / Line 22: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Kim, Y]]
 [[Category: Potluri, N]]

5sy5

From Proteopedia

Revision as of 11:14, 16 September 2020

Crystal Structure of the Heterodimeric NPAS1-ARNT Complex

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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