2g6f

Revision as of 11:52, 21 November 2007 by OCA (talk | contribs) (New page: left|200px<br /><applet load="2g6f" size="450" color="white" frame="true" align="right" spinBox="true" caption="2g6f, resolution 0.92Å" /> '''Crystal Structure of...)
(diff) ← Older revision | Latest revision (diff) | Newer revision → (diff)

Crystal Structure of the SH3 Domain of betaPIX in Complex with a High Affinity Peptide from PAK2

File:2g6f.gif


2g6f, resolution 0.92Å

Drag the structure with the mouse to rotate

OverviewOverview

The p21-activated kinases (PAKs) are important effector proteins of the, small GTPases Cdc42 and Rac and control cytoskeletal rearrangements and, cell proliferation. The direct interaction of PAKs with guanine nucleotide, exchange factors from the PIX/Cool family, which is responsible for the, localization of PAK kinases to focal complexes in the cell, is mediated by, a 24-residue peptide segment in PAKs and an N-terminal src homology 3, (SH3) domain in PIX/Cool. The SH3-binding segment of PAK contains the, atypical consensus-binding motif PxxxPR, which is required for unusually, high affinity binding. In order to understand the structural basis for the, high affinity and specificity of the PIX-PAK interaction, we solved, crystal structures for the N-terminal SH3 domain of betaPIX and for the, complex of the atypical binding segment of PAK2 with the N-terminal SH3, domain of betaPIX at 0.92 A and 1.3A resolution, respectively. The, asymmetric unit of the crystal contains two SH3 domains and two peptide, ligands. The bound peptide adopts a conformation that allows for intimate, contacts with three grooves on the surface of the SH3 domain that lie, between the n-Src and RT-loops. Most notably, the arginine residue of the, PxxxPR motif forms a salt-bridge and is tightly coordinated by a number of, residues in the SH3 domain. This arginine-specific interaction appears to, be the key determinant for the high affinity binding of PAK peptides., Furthermore, C-terminal residues of the peptide engage in additional, interactions with the surface of the RT-loop, which significantly, increases binding specificity. Compared to a recent NMR structure of a, similar complex, our crystal structure reveals an alternate binding mode., Finally, we compare our crystal structure with the recently published, betaPIX/Cbl-b complex structure, and suggest the existence of a molecular, switch.

About this StructureAbout this Structure

2G6F is a Single protein structure of sequence from Rattus norvegicus with NCO as ligand. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of the SH3 domain of betaPIX in complex with a high affinity peptide from PAK2., Hoelz A, Janz JM, Lawrie SD, Corwin B, Lee A, Sakmar TP, J Mol Biol. 2006 Apr 28;358(2):509-22. Epub 2006 Feb 28. PMID:16527308

Page seeded by OCA on Wed Nov 21 10:59:40 2007

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA