View source for 5nzz


==Crystal structure of phosphorylated p38aMAPK in complex with TAB1==
<StructureSection load='5nzz' size='340' side='right'caption='[[5nzz]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5nzz]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NZZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NZZ 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AGS:PHOSPHOTHIOPHOSPHORIC+ACID-ADENYLATE+ESTER'>AGS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=5nzz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nzz OCA], [https://pdbe.org/5nzz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nzz RCSB], [https://www.ebi.ac.uk/pdbsum/5nzz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nzz 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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Inhibiting MAPK14 (p38alpha) diminishes cardiac damage in myocardial ischemia. During myocardial ischemia, p38alpha interacts with TAB1, a scaffold protein, which promotes p38alpha autoactivation; active p38alpha (pp38alpha) then transphosphorylates TAB1. Previously, we solved the X-ray structure of the p38alpha-TAB1 (residues 384-412) complex. Here, we further characterize the interaction by solving the structure of the pp38alpha-TAB1 (residues 1-438) complex in the active state. Based on this information, we created a global knock-in (KI) mouse with substitution of 4 residues on TAB1 that we show are required for docking onto p38alpha. Whereas ablating p38alpha or TAB1 resulted in early embryonal lethality, the TAB1-KI mice were viable and had no appreciable alteration in their lymphocyte repertoire or myocardial transcriptional profile; nonetheless, following in vivo regional myocardial ischemia, infarction volume was significantly reduced and the transphosphorylation of TAB1 was disabled. Unexpectedly, the activation of myocardial p38alpha during ischemia was only mildly attenuated in TAB1-KI hearts. We also identified a group of fragments able to disrupt the interaction between p38alpha and TAB1. We conclude that the interaction between the 2 proteins can be targeted with small molecules. The data reveal that it is possible to selectively inhibit signaling downstream of p38alpha to attenuate ischemic injury.

The TAB1-p38alpha complex aggravates myocardial injury and can be targeted by small molecules.,De Nicola GF, Bassi R, Nichols C, Fernandez-Caggiano M, Golforoush PA, Thapa D, Anderson R, Martin ED, Verma S, Kleinjung J, Laing A, Hutchinson JP, Eaton P, Clark J, Marber MS JCI Insight. 2018 Aug 23;3(16). pii: 121144. doi: 10.1172/jci.insight.121144. PMID:30135318<ref>PMID:30135318</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5nzz" style="background-color:#fffaf0;"></div>

==See Also==
*[[Mitogen-activated protein kinase 3D structures|Mitogen-activated protein kinase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: De Nicola GF]]
[[Category: Nichols CE]]