2oza: Difference between revisions

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-[[Image:2oza.gif|left|200px]]<br />
-<applet load="2oza" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="2oza, resolution 2.700&Aring;" />
-'''Structure of p38alpha complex'''<br />
-==Overview==
+==Structure of p38alpha complex==
-p38 MAPK and MAPK-activated protein kinase 2 (MK2) are key components of, signaling pathways leading to many cellular responses, notably the, proinflammatory cytokine production. The physical association of p38alpha, isoform and MK2 is believed to be physiologically important for this, signaling. We report the 2.7-A resolution crystal structure of the, unphosphorylated complex between p38alpha and MK2. These protein kinases, bind "head-to-head," present their respective active sites on, approximately the same side of the heterodimer, and form extensive, intermolecular interactions. Among these interactions, the MK2, Ile-366-Ala-390, which includes the bipartite nuclear localization signal, binds to the p38alpha-docking region. This binding supports the, involvement of noncatalytic regions to the tight binding of the, MK2:p38alpha binary assembly. The MK2 residues 345-365, containing the, nuclear export signal, block access to the p38alpha active site. Some, regulatory phosphorylation regions of both protein kinases engage in, multiple interactions with one another in this complex. This structure, gives new insights into the regulation of the protein kinases p38alpha and, MK2, aids in the better understanding of their known cellular and, biochemical studies, and provides a basis for understanding other, regulatory protein-protein interactions involving signal transduction, proteins.
+<StructureSection load='2oza' size='340' side='right'caption='[[2oza]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2oza]] is a 2 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=2OZA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OZA 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]] 2.7&#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=2oza FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oza OCA], [https://pdbe.org/2oza PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2oza RCSB], [https://www.ebi.ac.uk/pdbsum/2oza PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2oza ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/MAPK2_HUMAN MAPK2_HUMAN] Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, ELAVL1, HNRNPA0, HSF1, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilize GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3.<ref>PMID:8280084</ref> <ref>PMID:8093612</ref> <ref>PMID:8774846</ref> <ref>PMID:10383393</ref> <ref>PMID:12456657</ref> <ref>PMID:11844797</ref> <ref>PMID:12565831</ref> <ref>PMID:14499342</ref> <ref>PMID:14517288</ref> <ref>PMID:15014438</ref> <ref>PMID:15629715</ref> <ref>PMID:16456544</ref> <ref>PMID:16278218</ref> <ref>PMID:17481585</ref> <ref>PMID:18021073</ref> <ref>PMID:20932473</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/oz/2oza_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=2oza ConSurf].
+<div style="clear:both"></div>
-==About this Structure==
+==See Also==
-OZA is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2OZA OCA].
+*[[Mitogen-activated protein kinase 3D structures|Mitogen-activated protein kinase 3D structures]]
+== References ==
-==Reference==
+<references/>
-Molecular basis of MAPK-activated protein kinase 2:p38 assembly., White A, Pargellis CA, Studts JM, Werneburg BG, Farmer BT 2nd, Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6353-8. Epub 2007 Mar 29. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17395714 17395714]
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
+[[Category: Large Structures]]
 [[Category: Mus musculus]]
-[[Category: Non-specific serine/threonine protein kinase]]
+[[Category: Farmer II BT]]
-[[Category: Protein complex]]
+[[Category: Pargellis CA]]
-[[Category: II, B.T.Farmer.]]
+[[Category: Studts JM]]
-[[Category: Pargellis, C.A.]]
+[[Category: Werneburg BG]]
-[[Category: Studts, J.M.]]
+[[Category: White A]]
-[[Category: Werneburg, B.G.]]
-[[Category: White, A.]]
-[[Category: mk2]]
-[[Category: p38a]]
-[[Category: protein-protein complex]]
-[[Category: serine/threonine kinase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 23:18:28 2007''