1ZSG

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

Summary for 1ZSG

• Entry DOI: 10.2210/pdb1zsg/pdb
• Descriptor: Rho guanine nucleotide exchange factor 7, Serine/threonine-protein kinase PAK 1 (2 entities in total)
• Functional Keywords: sh3-peptide complex, transferase
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: Q13153
• Total number of polymer chains: 2
• Total formula weight: 9922.90

Authors

Mott, H.R.,Nietlispach, D.,Evetts, K.A.,Owen, D. (deposition date: 2005-05-24, release date: 2005-08-30, Last modification date: 2024-05-22)

Primary citation

Mott, H.R.,Nietlispach, D.,Evetts, K.A.,Owen, D.
Structural Analysis of the SH3 Domain of beta-PIX and Its Interaction with alpha-p21 Activated Kinase (PAK)
Biochemistry, 44:10977-10983, 2005

PubMed Abstract: 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.

PubMed: 16101281
DOI: 10.1021/bi050374a

Experimental method

SOLUTION NMR