4xbu

From Proteopedia

(Difference between revisions)

Revision as of 07:14, 29 May 2019

In vitro Crystal Structure of PAK4 in complex with Inka peptide

Structural highlights

4xbu is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Related:	4xbr
Gene:	PAK4, KIAA1142 (HUMAN)
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PAK4_HUMAN] Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, growth, proliferation or cell survival. Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates and inactivates the protein phosphatase SSH1, leading to increased inhibitory phosphorylation of the actin binding/depolymerizing factor cofilin. Decreased cofilin activity may lead to stabilization of actin filaments. Phosphorylates LIMK1, a kinase that also inhibits the activity of cofilin. Phosphorylates integrin beta5/ITGB5 and thus regulates cell motility. Phosphorylates ARHGEF2 and activates the downstream target RHOA that plays a role in the regulation of assembly of focal adhesions and actin stress fibers. Stimulates cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Alternatively, inhibits apoptosis by preventing caspase-8 binding to death domain receptors in a kinase independent manner. Plays a role in cell-cycle progression by controlling levels of the cell-cycle regulatory protein CDKN1A and by phosphorylating RAN.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Publication Abstract from PubMed

PAK4 is a metazoan-specific kinase acting downstream of Cdc42. Here we describe the structure of human PAK4 in complex with Inka1, a potent endogenous kinase inhibitor. Using single mammalian cells containing crystals 50 mum in length, we have determined the in cellulo crystal structure at 2.95 A resolution, which reveals the details of how the PAK4 catalytic domain binds cellular ATP and the Inka1 inhibitor. The crystal lattice consists only of PAK4-PAK4 contacts, which form a hexagonal array with channels of 80 A in diameter that run the length of the crystal. The crystal accommodates a variety of other proteins when fused to the kinase inhibitor. Inka1-GFP was used to monitor the process crystal formation in living cells. Similar derivatives of Inka1 will allow us to study the effects of PAK4 inhibition in cells and model organisms, to allow better validation of therapeutic agents targeting PAK4.

An in cellulo-derived structure of PAK4 in complex with its inhibitor Inka1.,Baskaran Y, Ang KC, Anekal PV, Chan WL, Grimes JM, Manser E, Robinson RC Nat Commun. 2015 Nov 26;6:8681. doi: 10.1038/ncomms9681. PMID:26607847^[8]

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

References

↑ Gnesutta N, Qu J, Minden A. The serine/threonine kinase PAK4 prevents caspase activation and protects cells from apoptosis. J Biol Chem. 2001 Apr 27;276(17):14414-9. Epub 2001 Jan 24. PMID:11278822 doi:10.1074/jbc.M011046200
↑ Qu J, Cammarano MS, Shi Q, Ha KC, de Lanerolle P, Minden A. Activated PAK4 regulates cell adhesion and anchorage-independent growth. Mol Cell Biol. 2001 May;21(10):3523-33. PMID:11313478 doi:10.1128/MCB.21.10.3523-3533.2001
↑ Gnesutta N, Minden A. Death receptor-induced activation of initiator caspase 8 is antagonized by serine/threonine kinase PAK4. Mol Cell Biol. 2003 Nov;23(21):7838-48. PMID:14560027
↑ Soosairajah J, Maiti S, Wiggan O, Sarmiere P, Moussi N, Sarcevic B, Sampath R, Bamburg JR, Bernard O. Interplay between components of a novel LIM kinase-slingshot phosphatase complex regulates cofilin. EMBO J. 2005 Feb 9;24(3):473-86. Epub 2005 Jan 20. PMID:15660133 doi:7600543
↑ Li Z, Zhang H, Lundin L, Thullberg M, Liu Y, Wang Y, Claesson-Welsh L, Stromblad S. p21-activated kinase 4 phosphorylation of integrin beta5 Ser-759 and Ser-762 regulates cell migration. J Biol Chem. 2010 Jul 30;285(31):23699-710. doi: 10.1074/jbc.M110.123497. Epub, 2010 May 27. PMID:20507994 doi:10.1074/jbc.M110.123497
↑ Bompard G, Rabeharivelo G, Frank M, Cau J, Delsert C, Morin N. Subgroup II PAK-mediated phosphorylation regulates Ran activity during mitosis. J Cell Biol. 2010 Sep 6;190(5):807-22. doi: 10.1083/jcb.200912056. Epub 2010 Aug , 30. PMID:20805321 doi:10.1083/jcb.200912056
↑ Wallace SW, Durgan J, Jin D, Hall A. Cdc42 regulates apical junction formation in human bronchial epithelial cells through PAK4 and Par6B. Mol Biol Cell. 2010 Sep 1;21(17):2996-3006. doi: 10.1091/mbc.E10-05-0429. Epub, 2010 Jul 14. PMID:20631255 doi:10.1091/mbc.E10-05-0429
↑ Baskaran Y, Ang KC, Anekal PV, Chan WL, Grimes JM, Manser E, Robinson RC. An in cellulo-derived structure of PAK4 in complex with its inhibitor Inka1. Nat Commun. 2015 Nov 26;6:8681. doi: 10.1038/ncomms9681. PMID:26607847 doi:http://dx.doi.org/10.1038/ncomms9681

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4xbu"

@@ Line 1: / Line 1: @@
 ==In vitro Crystal Structure of PAK4 in complex with Inka peptide==
-<StructureSection load='4xbu' size='340' side='right' caption='[[4xbu]], [[Resolution|resolution]] 2.06&Aring;' scene=''>
+<StructureSection load='4xbu' size='340' side='right'caption='[[4xbu]], [[Resolution|resolution]] 2.06&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4xbu]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XBU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XBU FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4xbu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XBU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XBU FirstGlance]. <br>
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xbr|4xbr]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PAK4, KIAA1142 ([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=4xbu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xbu OCA], [http://pdbe.org/4xbu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xbu RCSB], [http://www.ebi.ac.uk/pdbsum/4xbu 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=4xbu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xbu OCA], [http://pdbe.org/4xbu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xbu RCSB], [http://www.ebi.ac.uk/pdbsum/4xbu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xbu ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 21: @@
 </div>
 <div class="pdbe-citations 4xbu" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Serine/threonine protein kinase|Serine/threonine protein kinase]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Non-specific serine/threonine protein kinase]]
 [[Category: Anekal, P V]]

4xbu

From Proteopedia

Revision as of 07:14, 29 May 2019

In vitro Crystal Structure of PAK4 in complex with Inka peptide

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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