3pcs

From Proteopedia

(Difference between revisions)

Revision as of 08:28, 11 August 2016

Structure of EspG-PAK2 autoinhibitory Ialpha3 helix complex

Structural highlights

3pcs is a 8 chain structure with sequence from Eco57 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	3pcr
Gene:	ECs4590, espG, Z5142 (ECO57), PAK2 (HUMAN)
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8]

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^[9]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Jakobi R, McCarthy CC, Koeppel MA, Stringer DK. Caspase-activated PAK-2 is regulated by subcellular targeting and proteasomal degradation. J Biol Chem. 2003 Oct 3;278(40):38675-85. Epub 2003 Jul 9. PMID:12853446 doi:http://dx.doi.org/10.1074/jbc.M306494200
↑ Orton KC, Ling J, Waskiewicz AJ, Cooper JA, Merrick WC, Korneeva NL, Rhoads RE, Sonenberg N, Traugh JA. Phosphorylation of Mnk1 by caspase-activated Pak2/gamma-PAK inhibits phosphorylation and interaction of eIF4G with Mnk. J Biol Chem. 2004 Sep 10;279(37):38649-57. Epub 2004 Jul 2. PMID:15234964 doi:http://dx.doi.org/10.1074/jbc.M407337200
↑ Vilas GL, Corvi MM, Plummer GJ, Seime AM, Lambkin GR, Berthiaume LG. Posttranslational myristoylation of caspase-activated p21-activated protein kinase 2 (PAK2) potentiates late apoptotic events. Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6542-7. Epub 2006 Apr 14. PMID:16617111 doi:http://dx.doi.org/0600824103
↑ Hsu RM, Tsai MH, Hsieh YJ, Lyu PC, Yu JS. Identification of MYO18A as a novel interacting partner of the PAK2/betaPIX/GIT1 complex and its potential function in modulating epithelial cell migration. Mol Biol Cell. 2010 Jan 15;21(2):287-301. doi: 10.1091/mbc.E09-03-0232. Epub 2009, Nov 18. PMID:19923322 doi:http://dx.doi.org/10.1091/mbc.E09-03-0232
↑ Li T, Zhang J, Zhu F, Wen W, Zykova T, Li X, Liu K, Peng C, Ma W, Shi G, Dong Z, Bode AM, Dong Z. P21-activated protein kinase (PAK2)-mediated c-Jun phosphorylation at 5 threonine sites promotes cell transformation. Carcinogenesis. 2011 May;32(5):659-66. doi: 10.1093/carcin/bgq271. Epub 2010 Dec , 22. PMID:21177766 doi:http://dx.doi.org/10.1093/carcin/bgq271
↑ De la Mota-Peynado A, Chernoff J, Beeser A. Identification of the atypical MAPK Erk3 as a novel substrate for p21-activated kinase (Pak) activity. J Biol Chem. 2011 Apr 15;286(15):13603-11. doi: 10.1074/jbc.M110.181743. Epub, 2011 Feb 11. PMID:21317288 doi:http://dx.doi.org/10.1074/jbc.M110.181743
↑ Kang B, Pu M, Hu G, Wen W, Dong Z, Zhao K, Stillman B, Zhang Z. Phosphorylation of H4 Ser 47 promotes HIRA-mediated nucleosome assembly. Genes Dev. 2011 Jul 1;25(13):1359-64. doi: 10.1101/gad.2055511. PMID:21724829 doi:http://dx.doi.org/10.1101/gad.2055511
↑ Rudel T, Bokoch GM. Membrane and morphological changes in apoptotic cells regulated by caspase-mediated activation of PAK2. Science. 1997 Jun 6;276(5318):1571-4. PMID:9171063
↑ 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3pcs"

@@ Line 1: / Line 1: @@
 ==Structure of EspG-PAK2 autoinhibitory Ialpha3 helix complex==
 <StructureSection load='3pcs' size='340' side='right' caption='[[3pcs]], [[Resolution|resolution]] 2.86&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3pcs]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [http://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 [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 [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>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3pcr|3pcr]]</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=562 Escherichia coli]), PAK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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='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://www.rcsb.org/pdb/explore.do?structureId=3pcs RCSB], [http://www.ebi.ac.uk/pdbsum/3pcs PDBsum]</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>
+== 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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 16: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3pcs" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Escherichia coli]]
+[[Category: Eco57]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Non-specific serine/threonine protein kinase]]
 [[Category: Alto, N M]]

3pcs

From Proteopedia

Revision as of 08:28, 11 August 2016

Structure of EspG-PAK2 autoinhibitory Ialpha3 helix complex

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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