6zr5: Difference between revisions

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OCA

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-'''Unreleased structure'''
-The entry 6zr5 is ON HOLD
+==Crystal structure of JNK1 in complex with ATF2(19-58)==
+<StructureSection load='6zr5' size='340' side='right'caption='[[6zr5]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6zr5]] is a 4 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=6ZR5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZR5 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]] 2.699&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6zr5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zr5 OCA], [https://pdbe.org/6zr5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zr5 RCSB], [https://www.ebi.ac.uk/pdbsum/6zr5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zr5 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/MK08_HUMAN MK08_HUMAN] Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone. Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH.<ref>PMID:16581800</ref> <ref>PMID:17296730</ref> <ref>PMID:18307971</ref> <ref>PMID:18570871</ref> <ref>PMID:20027304</ref> <ref>PMID:21364637</ref> <ref>PMID:21095239</ref> <ref>PMID:21856198</ref>   JNK1 isoforms display different binding patterns: beta-1 preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta-2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms.<ref>PMID:16581800</ref> <ref>PMID:17296730</ref> <ref>PMID:18307971</ref> <ref>PMID:18570871</ref> <ref>PMID:20027304</ref> <ref>PMID:21364637</ref> <ref>PMID:21095239</ref> <ref>PMID:21856198</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Transcription factor phosphorylation at specific sites often activates gene expression, but how environmental cues quantitatively control transcription is not well-understood. Activating protein 1 transcription factors are phosphorylated by mitogen-activated protein kinases (MAPK) in their transactivation domains (TAD) at so-called phosphoswitches, which are a hallmark in response to growth factors, cytokines or stress. We show that the ATF2 TAD is controlled by functionally distinct signaling pathways (JNK and p38) through structurally different MAPK binding sites. Moreover, JNK mediated phosphorylation at an evolutionarily more recent site diminishes p38 binding and made the phosphoswitch differently sensitive to JNK and p38 in vertebrates. Structures of MAPK-TAD complexes and mechanistic modeling of ATF2 TAD phosphorylation in cells suggest that kinase binding motifs and phosphorylation sites line up to maximize MAPK based co-regulation. This study shows how the activity of an ancient transcription controlling phosphoswitch became dependent on the relative flux of upstream signals.
-Authors: Kirsch, K., Zeke, A., Remenyi, A.
+Co-regulation of the transcription controlling ATF2 phosphoswitch by JNK and p38.,Kirsch K, Zeke A, Toke O, Sok P, Sethi A, Sebo A, Kumar GS, Egri P, Poti AL, Gooley P, Peti W, Bento I, Alexa A, Remenyi A Nat Commun. 2020 Nov 13;11(1):5769. doi: 10.1038/s41467-020-19582-3. PMID:33188182<ref>PMID:33188182</ref>
-Description: Crystal structure of JNK1 in complex with ATF2(19-58)
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Kirsch, K]]
+<div class="pdbe-citations 6zr5" style="background-color:#fffaf0;"></div>
-[[Category: Remenyi, A]]
-[[Category: Zeke, A]]
+==See Also==
+*[[Mitogen-activated protein kinase 3D structures|Mitogen-activated protein kinase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Kirsch K]]
+[[Category: Remenyi A]]
+[[Category: Zeke A]]