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[[Image:1zsg.gif|left|200px]]


{{Structure
==beta PIX-SH3 complexed with an atypical peptide from alpha-PAK==
|PDB= 1zsg |SIZE=350|CAPTION= <scene name='initialview01'>1zsg</scene>
<StructureSection load='1zsg' size='340' side='right'caption='[[1zsg]]' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND=  
<table><tr><td colspan='2'>[[1zsg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZSG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZSG FirstGlance]. <br>
|ACTIVITY= <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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
|GENE= ARHGEF7, COOL1, KIAA0142, P85SPR, PAK3BP, PIXB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1zsg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zsg OCA], [https://pdbe.org/1zsg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zsg RCSB], [https://www.ebi.ac.uk/pdbsum/1zsg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zsg ProSAT]</span></td></tr>
|DOMAIN=
</table>
|RELATEDENTRY=
== Function ==
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1zsg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zsg OCA], [http://www.ebi.ac.uk/pdbsum/1zsg PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1zsg RCSB]</span>
[https://www.uniprot.org/uniprot/ARHG7_HUMAN ARHG7_HUMAN] Acts as a RAC1 guanine nucleotide exchange factor (GEF) and can induce membrane ruffling. Functions in cell migration, attachment and cell spreading. Promotes targeting of RAC1 to focal adhesions (By similarity). May function as a positive regulator of apoptosis. Downstream of NMDA receptors and CaMKK-CaMK1 signaling cascade, promotes the formation of spines and synapses in hippocampal neurons.<ref>PMID:19041750</ref> <ref>PMID:18716323</ref> <ref>PMID:18184567</ref>
}}
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zs/1zsg_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1zsg ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The PAK Ser/Thr kinases are important downstream effectors of the Rho family GTPases Cdc42 and Rac, partly mediating the role of these G proteins in cell proliferation and cytoskeletal rearrangements. As well as small G proteins, PAK interacts with the Cdc42/Rac exchange factor beta-PIX via the PIX SH3 domain and a nontypical Pro-rich region in PAK. This interaction is thought to affect the localization of PAK, as well as increased GTP/GDP exchange of Rac and Cdc42. We have determined the structure of the PIX-SH3/PAK peptide complex and shown that it differs from typical Src-like SH3/peptide complexes. The peptide makes contacts through the Pro-rich sequence in a similar way to standard SH3/peptide complexes, even though the Pro residue positions are not conserved. In addition, there are interactions with a Pro and Lys in the PAK, which are C-terminal to the conserved Arg found in all SH3-binding sequences. These contact a fourth binding pocket on the SH3 domain. We have measured the affinity of PIX-SH3 for the PAK peptide and found that it is of intermediate affinity. When PAK is activated, Ser-199 in the PIX-binding site is phosphorylated. This phosphorylation is sufficient to reduce the affinity for PIX 6-fold.


'''beta PIX-SH3 complexed with an atypical peptide from alpha-PAK'''
Structural analysis of the SH3 domain of beta-PIX and its interaction with alpha-p21 activated kinase (PAK).,Mott HR, Nietlispach D, Evetts KA, Owen D Biochemistry. 2005 Aug 23;44(33):10977-83. PMID:16101281<ref>PMID:16101281</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1zsg" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
The PAK Ser/Thr kinases are important downstream effectors of the Rho family GTPases Cdc42 and Rac, partly mediating the role of these G proteins in cell proliferation and cytoskeletal rearrangements. As well as small G proteins, PAK interacts with the Cdc42/Rac exchange factor beta-PIX via the PIX SH3 domain and a nontypical Pro-rich region in PAK. This interaction is thought to affect the localization of PAK, as well as increased GTP/GDP exchange of Rac and Cdc42. We have determined the structure of the PIX-SH3/PAK peptide complex and shown that it differs from typical Src-like SH3/peptide complexes. The peptide makes contacts through the Pro-rich sequence in a similar way to standard SH3/peptide complexes, even though the Pro residue positions are not conserved. In addition, there are interactions with a Pro and Lys in the PAK, which are C-terminal to the conserved Arg found in all SH3-binding sequences. These contact a fourth binding pocket on the SH3 domain. We have measured the affinity of PIX-SH3 for the PAK peptide and found that it is of intermediate affinity. When PAK is activated, Ser-199 in the PIX-binding site is phosphorylated. This phosphorylation is sufficient to reduce the affinity for PIX 6-fold.
*[[Rho guanine nucleotide exchange factor 3D structures|Rho guanine nucleotide exchange factor 3D structures]]
 
== References ==
==About this Structure==
<references/>
1ZSG is a [[Protein complex]] structure of sequences 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=1ZSG OCA].
__TOC__
 
</StructureSection>
==Reference==
Structural analysis of the SH3 domain of beta-PIX and its interaction with alpha-p21 activated kinase (PAK)., Mott HR, Nietlispach D, Evetts KA, Owen D, Biochemistry. 2005 Aug 23;44(33):10977-83. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16101281 16101281]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Large Structures]]
[[Category: Protein complex]]
[[Category: Evetts KA]]
[[Category: Evetts, K A.]]
[[Category: Mott HR]]
[[Category: Mott, H R.]]
[[Category: Nietlispach D]]
[[Category: Nietlispach, D.]]
[[Category: Owen D]]
[[Category: Owen, D.]]
[[Category: sh3-peptide complex]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:41:03 2008''

Latest revision as of 11:12, 15 May 2024

beta PIX-SH3 complexed with an atypical peptide from alpha-PAKbeta PIX-SH3 complexed with an atypical peptide from alpha-PAK

Structural highlights

1zsg is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ARHG7_HUMAN Acts as a RAC1 guanine nucleotide exchange factor (GEF) and can induce membrane ruffling. Functions in cell migration, attachment and cell spreading. Promotes targeting of RAC1 to focal adhesions (By similarity). May function as a positive regulator of apoptosis. Downstream of NMDA receptors and CaMKK-CaMK1 signaling cascade, promotes the formation of spines and synapses in hippocampal neurons.[1] [2] [3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The PAK Ser/Thr kinases are important downstream effectors of the Rho family GTPases Cdc42 and Rac, partly mediating the role of these G proteins in cell proliferation and cytoskeletal rearrangements. As well as small G proteins, PAK interacts with the Cdc42/Rac exchange factor beta-PIX via the PIX SH3 domain and a nontypical Pro-rich region in PAK. This interaction is thought to affect the localization of PAK, as well as increased GTP/GDP exchange of Rac and Cdc42. We have determined the structure of the PIX-SH3/PAK peptide complex and shown that it differs from typical Src-like SH3/peptide complexes. The peptide makes contacts through the Pro-rich sequence in a similar way to standard SH3/peptide complexes, even though the Pro residue positions are not conserved. In addition, there are interactions with a Pro and Lys in the PAK, which are C-terminal to the conserved Arg found in all SH3-binding sequences. These contact a fourth binding pocket on the SH3 domain. We have measured the affinity of PIX-SH3 for the PAK peptide and found that it is of intermediate affinity. When PAK is activated, Ser-199 in the PIX-binding site is phosphorylated. This phosphorylation is sufficient to reduce the affinity for PIX 6-fold.

Structural analysis of the SH3 domain of beta-PIX and its interaction with alpha-p21 activated kinase (PAK).,Mott HR, Nietlispach D, Evetts KA, Owen D Biochemistry. 2005 Aug 23;44(33):10977-83. PMID:16101281[4]

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

See Also

References

  1. ↑ Zhan L, Rosenberg A, Bergami KC, Yu M, Xuan Z, Jaffe AB, Allred C, Muthuswamy SK. Deregulation of scribble promotes mammary tumorigenesis and reveals a role for cell polarity in carcinoma. Cell. 2008 Nov 28;135(5):865-78. doi: 10.1016/j.cell.2008.09.045. PMID:19041750 doi:10.1016/j.cell.2008.09.045
  2. ↑ Nola S, Sebbagh M, Marchetto S, Osmani N, Nourry C, Audebert S, Navarro C, Rachel R, Montcouquiol M, Sans N, Etienne-Manneville S, Borg JP, Santoni MJ. Scrib regulates PAK activity during the cell migration process. Hum Mol Genet. 2008 Nov 15;17(22):3552-65. doi: 10.1093/hmg/ddn248. Epub 2008 Aug, 20. PMID:18716323 doi:10.1093/hmg/ddn248
  3. ↑ Saneyoshi T, Wayman G, Fortin D, Davare M, Hoshi N, Nozaki N, Natsume T, Soderling TR. Activity-dependent synaptogenesis: regulation by a CaM-kinase kinase/CaM-kinase I/betaPIX signaling complex. Neuron. 2008 Jan 10;57(1):94-107. doi: 10.1016/j.neuron.2007.11.016. PMID:18184567 doi:http://dx.doi.org/10.1016/j.neuron.2007.11.016
  4. ↑ Mott HR, Nietlispach D, Evetts KA, Owen D. Structural analysis of the SH3 domain of beta-PIX and its interaction with alpha-p21 activated kinase (PAK). Biochemistry. 2005 Aug 23;44(33):10977-83. PMID:16101281 doi:10.1021/bi050374a
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