2j4o: Difference between revisions

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[[Image:2j4o.jpg|left|200px]]<br /><applet load="2j4o" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2j4o, resolution 2.25&Aring;" />
'''STRUCTURE OF TAB1'''<br />


==Overview==
==Structure of TAB1==
TAB1 [TAK1 (transforming growth factor-beta-activated kinase 1)-binding, protein 1] is one of the regulatory subunits of TAK1, a protein kinase, that lies at the head of three pro-inflammatory kinase cascades. In the, current study we report the crystal structure of the N-terminal domain of, TAB1. Surprisingly, TAB1 possesses a fold closely related to that of the, PPM (Mg2+- or Mn2+-dependent protein phosphatase) family as demonstrated, by the close structural similarity with protein phosphatase 2C alpha., However, we were unable to detect any phosphatase activity for TAB1 using, a phosphopeptide or p-nitrophenyl phosphate as substrate. Although the, overall protein phosphatase 2C alpha fold is conserved in TAB1, detailed, structural analyses and mutagenesis studies show that several key residues, required for dual metal-binding and catalysis are not present in TAB1, although binding of a single metal is supported by soaking experiments, with manganese and isothermal titration calorimetry. Thus, it appears that, TAB1 is a 'pseudophosphatase', possibly binding to and regulating, accessibility of phosphorylated residues on substrates downstream of TAK1, or on the TAK1 complex itself.
<StructureSection load='2j4o' size='340' side='right'caption='[[2j4o]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2j4o]] is a 1 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=2J4O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J4O FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25&#8491;</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=2j4o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j4o OCA], [https://pdbe.org/2j4o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j4o RCSB], [https://www.ebi.ac.uk/pdbsum/2j4o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j4o ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TAB1_HUMAN TAB1_HUMAN] May be an important signaling intermediate between TGFB receptors and MAP3K7/TAK1. May play an important role in mammalian embryogenesis.<ref>PMID:16879102</ref>
== 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/j4/2j4o_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=2j4o ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
TAB1 [TAK1 (transforming growth factor-beta-activated kinase 1)-binding protein 1] is one of the regulatory subunits of TAK1, a protein kinase that lies at the head of three pro-inflammatory kinase cascades. In the current study we report the crystal structure of the N-terminal domain of TAB1. Surprisingly, TAB1 possesses a fold closely related to that of the PPM (Mg2+- or Mn2+-dependent protein phosphatase) family as demonstrated by the close structural similarity with protein phosphatase 2C alpha. However, we were unable to detect any phosphatase activity for TAB1 using a phosphopeptide or p-nitrophenyl phosphate as substrate. Although the overall protein phosphatase 2C alpha fold is conserved in TAB1, detailed structural analyses and mutagenesis studies show that several key residues required for dual metal-binding and catalysis are not present in TAB1, although binding of a single metal is supported by soaking experiments with manganese and isothermal titration calorimetry. Thus, it appears that TAB1 is a 'pseudophosphatase', possibly binding to and regulating accessibility of phosphorylated residues on substrates downstream of TAK1 or on the TAK1 complex itself.


==About this Structure==
TAK1-binding protein 1 is a pseudophosphatase.,Conner SH, Kular G, Peggie M, Shepherd S, Schuttelkopf AW, Cohen P, Van Aalten DM Biochem J. 2006 Nov 1;399(3):427-34. PMID:16879102<ref>PMID:16879102</ref>
2J4O is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J4O OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
TAK1-binding protein 1 is a pseudophosphatase., Conner SH, Kular G, Peggie M, Shepherd S, Schuttelkopf AW, Cohen P, Van Aalten DM, Biochem J. 2006 Nov 1;399(3):427-34. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16879102 16879102]
</div>
<div class="pdbe-citations 2j4o" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Aalten, D.Van.]]
[[Category: Van Aalten D]]
[[Category: protein binding]]
[[Category: pseudo-phosphatase]]
[[Category: tak1 binding protein]]
[[Category: tgf-beta]]
 
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