2k27: Difference between revisions
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< | ==Solution structure of Human Pax8 Paired Box Domain== | ||
The | <StructureSection load='2k27' size='340' side='right'caption='[[2k27]]' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2k27]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K27 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K27 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2k27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k27 OCA], [https://pdbe.org/2k27 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k27 RCSB], [https://www.ebi.ac.uk/pdbsum/2k27 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k27 ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/PAX8_HUMAN PAX8_HUMAN] Defects in PAX8 are the cause of congenital hypothyroidism non-goitrous type 2 (CHNG2) [MIM:[https://omim.org/entry/218700 218700]. CHNG2 is a disease characterized by thyroid dysgenesis, the most frequent cause of congenital hypothyroidism, accounting for 85% of case. The thyroid gland can be completely absent (athyreosis), ectopically located and/or severely hypoplastic. Ectopic thyroid gland is the most frequent malformation, with thyroid tissue being found most often at the base of the tongue.<ref>PMID:9590296</ref> <ref>PMID:11232006</ref> <ref>PMID:11502839</ref> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PAX8_HUMAN PAX8_HUMAN] Transcription factor for the thyroid-specific expression of the genes exclusively expressed in the thyroid cell type, maintaining the functional differentiation of such cells. | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k2/2k27_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<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/main_output.php?pdb_ID=2k27 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Pax-8 is a transcription factor belonging to the PAX genes superfamily and its crucial role has been proven both in embryo and in the adult organism. Pax-8 activity is regulated via a redox-based mechanism centered on the glutathionylation of specific cysteines in the N-terminal region (Cys45 and Cys57). These residues belong to a highly evolutionary conserved DNA binding site: the Paired Box (Prd) domain. Crystallographic protein-DNA complexes of the homologues Pax-6 and Pax-5 showed a bipartite Prd domain consisting of two helix-turn-helix (HTH) motifs separated by an extended linker region. Here, by means of nuclear magnetic resonance, we show for the first time that the HTH motifs are largely defined in the unbound Pax-8 Prd domain. Our findings contrast with previous induced fit models, in which Pax-8 is supposed to largely fold upon DNA binding. Importantly, our data provide the structural basis for the enhanced chemical reactivity of residues Cys45 and Cys57 and explain clinical missense mutations that are not obviously related to the DNA binding interface of the paired box domain. Finally, sequence conservation suggests that our findings could be a general feature of the Pax family transcription factors. | |||
The solution structure of DNA-free Pax-8 paired box domain accounts for redox regulation of transcriptional activity in the pax protein family.,Codutti L, van Ingen H, Vascotto C, Fogolari F, Corazza A, Tell G, Quadrifoglio F, Viglino P, Boelens R, Esposito G J Biol Chem. 2008 Nov 28;283(48):33321-8. Epub 2008 Sep 30. PMID:18829450<ref>PMID:18829450</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2k27" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Paired box protein|Paired box protein]] | |||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Boelens | [[Category: Boelens R]] | ||
[[Category: Codutti | [[Category: Codutti L]] | ||
[[Category: Corazza | [[Category: Corazza A]] | ||
[[Category: Esposito | [[Category: Esposito G]] | ||
[[Category: Fogolari | [[Category: Fogolari F]] | ||
[[Category: Quadrifoglio F]] | |||
[[Category: Quadrifoglio | [[Category: Tell G]] | ||
[[Category: Tell | [[Category: Vascotto C]] | ||
[[Category: Vascotto | [[Category: Viglino P]] | ||
[[Category: Viglino | [[Category: Van Ingen H]] | ||
[[Category: | |||
Latest revision as of 12:43, 9 May 2024
Solution structure of Human Pax8 Paired Box DomainSolution structure of Human Pax8 Paired Box Domain
Structural highlights
DiseasePAX8_HUMAN Defects in PAX8 are the cause of congenital hypothyroidism non-goitrous type 2 (CHNG2) [MIM:218700. CHNG2 is a disease characterized by thyroid dysgenesis, the most frequent cause of congenital hypothyroidism, accounting for 85% of case. The thyroid gland can be completely absent (athyreosis), ectopically located and/or severely hypoplastic. Ectopic thyroid gland is the most frequent malformation, with thyroid tissue being found most often at the base of the tongue.[1] [2] [3] FunctionPAX8_HUMAN Transcription factor for the thyroid-specific expression of the genes exclusively expressed in the thyroid cell type, maintaining the functional differentiation of such cells. 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 PubMedPax-8 is a transcription factor belonging to the PAX genes superfamily and its crucial role has been proven both in embryo and in the adult organism. Pax-8 activity is regulated via a redox-based mechanism centered on the glutathionylation of specific cysteines in the N-terminal region (Cys45 and Cys57). These residues belong to a highly evolutionary conserved DNA binding site: the Paired Box (Prd) domain. Crystallographic protein-DNA complexes of the homologues Pax-6 and Pax-5 showed a bipartite Prd domain consisting of two helix-turn-helix (HTH) motifs separated by an extended linker region. Here, by means of nuclear magnetic resonance, we show for the first time that the HTH motifs are largely defined in the unbound Pax-8 Prd domain. Our findings contrast with previous induced fit models, in which Pax-8 is supposed to largely fold upon DNA binding. Importantly, our data provide the structural basis for the enhanced chemical reactivity of residues Cys45 and Cys57 and explain clinical missense mutations that are not obviously related to the DNA binding interface of the paired box domain. Finally, sequence conservation suggests that our findings could be a general feature of the Pax family transcription factors. The solution structure of DNA-free Pax-8 paired box domain accounts for redox regulation of transcriptional activity in the pax protein family.,Codutti L, van Ingen H, Vascotto C, Fogolari F, Corazza A, Tell G, Quadrifoglio F, Viglino P, Boelens R, Esposito G J Biol Chem. 2008 Nov 28;283(48):33321-8. Epub 2008 Sep 30. PMID:18829450[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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