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| | ==Structure of EspG-PAK2 autoinhibitory Ialpha3 helix complex== | | ==Structure of EspG-PAK2 autoinhibitory Ialpha3 helix complex== |
| - | <StructureSection load='3pcs' size='340' side='right' caption='[[3pcs]], [[Resolution|resolution]] 2.86Å' scene=''> | + | <StructureSection load='3pcs' size='340' side='right'caption='[[3pcs]], [[Resolution|resolution]] 2.86Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3pcs]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Eco57 Eco57] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PCS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PCS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3pcs]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_O157:H7 Escherichia coli O157:H7] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PCS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PCS FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3pcr|3pcr]]</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]] 2.86Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ECs4590, espG, Z5142 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83334 ECO57]), PAK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3pcs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pcs OCA], [https://pdbe.org/3pcs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pcs RCSB], [https://www.ebi.ac.uk/pdbsum/3pcs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pcs 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/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] </span></td></tr>
| + | |
| - | <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=3pcs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pcs OCA], [http://pdbe.org/3pcs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3pcs RCSB], [http://www.ebi.ac.uk/pdbsum/3pcs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3pcs ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PAK2_HUMAN PAK2_HUMAN]] Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell motility, cell cycle progression, apoptosis or proliferation. Acts as downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Full-length PAK2 stimulates cell survival and cell growth. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Phosphorylates JUN and plays an important role in EGF-induced cell proliferation. Phosphorylates many other substrates including histone H4 to promote assembly of H3.3 and H4 into nucleosomes, BAD, ribosomal protein S6, or MBP. Additionally, associates with ARHGEF7 and GIT1 to perform kinase-independent functions such as spindle orientation control during mitosis. On the other hand, apoptotic stimuli such as DNA damage lead to caspase-mediated cleavage of PAK2, generating PAK-2p34, an active p34 fragment that translocates to the nucleus and promotes cellular apoptosis involving the JNK signaling pathway. Caspase-activated PAK2 phosphorylates MKNK1 and reduces cellular translation.<ref>PMID:12853446</ref> <ref>PMID:15234964</ref> <ref>PMID:16617111</ref> <ref>PMID:19923322</ref> <ref>PMID:21177766</ref> <ref>PMID:21317288</ref> <ref>PMID:21724829</ref> <ref>PMID:9171063</ref> | + | [https://www.uniprot.org/uniprot/Q7DB50_ECO57 Q7DB50_ECO57] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Eco57]] | + | [[Category: Escherichia coli O157:H7]] |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Non-specific serine/threonine protein kinase]] | + | [[Category: Large Structures]] |
| - | [[Category: Alto, N M]] | + | [[Category: Alto NM]] |
| - | [[Category: Selyunin, A S]] | + | [[Category: Selyunin AS]] |
| - | [[Category: Tomchick, D R]] | + | [[Category: Tomchick DR]] |
| - | [[Category: Autoinhibitory ialpha3 helix]]
| + | |
| - | [[Category: Bacterial effector]]
| + | |
| - | [[Category: Kinase]]
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| - | [[Category: Protein transport-transferase complex]]
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| Structural highlights
Function
Q7DB50_ECO57
Publication Abstract from PubMed
The fidelity and specificity of information flow within a cell is controlled by scaffolding proteins that assemble and link enzymes into signalling circuits. These circuits can be inhibited by bacterial effector proteins that post-translationally modify individual pathway components. However, there is emerging evidence that pathogens directly organize higher-order signalling networks through enzyme scaffolding, and the identity of the effectors and their mechanisms of action are poorly understood. Here we identify the enterohaemorrhagic Escherichia coli O157:H7 type III effector EspG as a regulator of endomembrane trafficking using a functional screen, and report ADP-ribosylation factor (ARF) GTPases and p21-activated kinases (PAKs) as its relevant host substrates. The 2.5 A crystal structure of EspG in complex with ARF6 shows how EspG blocks GTPase-activating-protein-assisted GTP hydrolysis, revealing a potent mechanism of GTPase signalling inhibition at organelle membranes. In addition, the 2.8 A crystal structure of EspG in complex with the autoinhibitory Ialpha3-helix of PAK2 defines a previously unknown catalytic site in EspG and provides an allosteric mechanism of kinase activation by a bacterial effector. Unexpectedly, ARF and PAKs are organized on adjacent surfaces of EspG, indicating its role as a 'catalytic scaffold' that effectively reprograms cellular events through the functional assembly of GTPase-kinase signalling complex.
The assembly of a GTPase-kinase signalling complex by a bacterial catalytic scaffold.,Selyunin AS, Sutton SE, Weigele BA, Reddick LE, Orchard RC, Bresson SM, Tomchick DR, Alto NM Nature. 2010 Dec 19. PMID:21170023[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Selyunin AS, Sutton SE, Weigele BA, Reddick LE, Orchard RC, Bresson SM, Tomchick DR, Alto NM. The assembly of a GTPase-kinase signalling complex by a bacterial catalytic scaffold. Nature. 2010 Dec 19. PMID:21170023 doi:10.1038/nature09593
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