3U3F

Structural basis for the interaction of Pyk2 PAT domain with paxillin LD motifs

Summary for 3U3F

• Entry DOI: 10.2210/pdb3u3f/pdb
• Related: 3U3C
• Descriptor: Protein-tyrosine kinase 2-beta, Paxillin LD2 peptide (3 entities in total)
• Functional Keywords: 4-helix bundle, focal adhesion, tyrosine kinase, paxillin, transferase-signaling protein complex, transferase/signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: Q14289; Cytoplasm, cytoskeleton : P49023
• Total number of polymer chains: 10
• Total formula weight: 72533.10

Authors

Vanarotti, M.,Miller, D.J.,Guibao, C.C.,Zheng, J.J. (deposition date: 2011-10-05, release date: 2012-10-24, Last modification date: 2023-09-13)

Primary citation

Vanarotti, M.S.,Miller, D.J.,Guibao, C.D.,Nourse, A.,Zheng, J.J.
Structural and Mechanistic Insights into the Interaction between Pyk2 and Paxillin LD Motifs.
J.Mol.Biol., 426:3985-4001, 2014

PubMed Abstract: Proline-rich tyrosine kinase 2 (Pyk2) is a member of the focal adhesion kinase (FAK) subfamily of cytoplasmic tyrosine kinases. The C-terminal Pyk2-focal adhesion targeting (FAT) domain binds to paxillin, an adhesion molecule. Paxillin has five leucine-aspartate (LD) motifs (LD1-LD5). Here, we show that the second LD motif of paxillin, LD2, interacts with Pyk2-FAT, similar to the known Pyk2-FAT/LD4 interaction. Both LD motifs can target two ligand binding sites on Pyk2-FAT. Interestingly, they also share similar binding affinity for Pyk2-FAT with preferential association to one site relative to the other. Nevertheless, the LD2-LD4 region of paxillin (paxillin(133-290)) binds to Pyk2-FAT as a 1:1 complex. However, our data suggest that the Pyk2-FAT and paxillin complex is dynamic and it appears to be a mixture of two distinct conformations of paxillin that almost equally compete for Pyk2-FAT binding. These studies provide insight into the underlying selectivity of paxillin for Pyk2 and FAK that may influence the differing behavior of these two closely related kinases in focal adhesion sites.

PubMed: 25174335
DOI: 10.1016/j.jmb.2014.08.014

Experimental method

X-RAY DIFFRACTION (3.101 Å)