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| ==Crystal structure of the ERK5 kinase domain in complex with an MKK5 binding fragment== | | ==Crystal structure of the ERK5 kinase domain in complex with an MKK5 binding fragment== |
| <StructureSection load='4ic7' size='340' side='right' caption='[[4ic7]], [[Resolution|resolution]] 2.60Å' scene=''> | | <StructureSection load='4ic7' size='340' side='right'caption='[[4ic7]], [[Resolution|resolution]] 2.60Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[4ic7]] is a 4 chain structure with 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=4IC7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IC7 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[4ic7]] 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=4IC7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IC7 FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ic8|4ic8]]</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></td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAPK7, BMK1, ERK5, PRKM7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), MAP2K5, MEK5, MKK5, PRKMK5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4ic7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ic7 OCA], [https://pdbe.org/4ic7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ic7 RCSB], [https://www.ebi.ac.uk/pdbsum/4ic7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ic7 ProSAT]</span></td></tr> |
| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </span></td></tr>
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| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ic7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ic7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ic7 RCSB], [http://www.ebi.ac.uk/pdbsum/4ic7 PDBsum]</span></td></tr> | |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/MK07_HUMAN MK07_HUMAN]] Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction.<ref>PMID:9384584</ref> <ref>PMID:9790194</ref> <ref>PMID:11254654</ref> <ref>PMID:11278431</ref> <ref>PMID:22869143</ref> [[http://www.uniprot.org/uniprot/MP2K5_HUMAN MP2K5_HUMAN]] Acts as a scaffold for the formation of a ternary MAP3K2/MAP3K3-MAP3K5-MAPK7 signaling complex. Activation of this pathway appears to play a critical role in protecting cells from stress-induced apoptosis, neuronal survival and cardiac development and angiogenesis.<ref>PMID:7759517</ref> <ref>PMID:9384584</ref> | | [https://www.uniprot.org/uniprot/MK07_HUMAN MK07_HUMAN] Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction.<ref>PMID:9384584</ref> <ref>PMID:9790194</ref> <ref>PMID:11254654</ref> <ref>PMID:11278431</ref> <ref>PMID:22869143</ref> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Mitogen-activated protein kinase (MAPK) activation depends on a linear binding motif found in all MAPK kinases (MKK). In addition, the PB1 (Phox and Bem1) domain of MKK5 is required for extracellular signal regulated kinase 5 (ERK5) activation. We present the crystal structure of ERK5 in complex with an MKK5 construct comprised of the PB1 domain and the linear binding motif. We show that ERK5 has distinct protein-protein interaction surfaces compared with ERK2, which is the closest ERK5 paralog. The two MAPKs have characteristically different physiological functions and their distinct protein-protein interaction surface topography enables them to bind different sets of activators and substrates. Structural and biochemical characterization revealed that the MKK5 PB1 domain cooperates with the MAPK binding linear motif to achieve substrate specific binding, and it also enables co-recruitment of the upstream activating enzyme and the downstream substrate into one signaling competent complex. Studies on present day MAPKs and MKKs hint on the way protein kinase networks may evolve. In particular, they suggest how paralogous enzymes with similar catalytic properties could acquire novel signaling roles by merely changing the way they make physical links to other proteins.
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| Structural mechanism for the specific assembly and activation of the extracellular signal regulated kinase 5 (ERK5) module.,Glatz G, Gogl G, Alexa A, Remenyi A J Biol Chem. 2013 Mar 22;288(12):8596-609. doi: 10.1074/jbc.M113.452235. Epub, 2013 Feb 4. PMID:23382384<ref>PMID:23382384</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| ==See Also== | | ==See Also== |
| *[[Mitogen-activated protein kinase|Mitogen-activated protein kinase]] | | *[[Mitogen-activated protein kinase 3D structures|Mitogen-activated protein kinase 3D structures]] |
| | *[[Mitogen-activated protein kinase kinase 3D structures|Mitogen-activated protein kinase kinase 3D structures]] |
| == References == | | == References == |
| <references/> | | <references/> |
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| </StructureSection> | | </StructureSection> |
| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| [[Category: Mitogen-activated protein kinase]] | | [[Category: Large Structures]] |
| [[Category: Gogl, G]] | | [[Category: Gogl G]] |
| [[Category: Remenyi, A]] | | [[Category: Remenyi A]] |
| [[Category: Kinase domain]]
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| [[Category: Signaling protein complex]]
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| [[Category: Transferase]]
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