1zsg: Difference between revisions

Revision as of 18:01, 3 May 2008

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

OverviewOverview

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.

About this StructureAbout this Structure

1ZSG is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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 Page seeded by OCA on Sat May 3 18:01:05 2008

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OCA

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 [[Image:1zsg.gif|left|200px]]
- {{Structure
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-|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>
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-|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])
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-|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>
-}}
 '''beta PIX-SH3 complexed with an atypical peptide from alpha-PAK'''
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 [[Category: Nietlispach, D.]]
 [[Category: Owen, D.]]
-[[Category: sh3-peptide complex]]
+[[Category: Sh3-peptide complex]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 18:01:05 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:41:03 2008''