Crystal Structures of Free and Ligand-Bound Focal Adhesion Targeting Domain of Pyk2

Journal Article · Thu Jan 01 04:00:00 EST 2009 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2009.04.011· OSTI ID:980114

Lulo, J; Yuzawa, S; Schlessinger, J

Focal adhesion targeting (FAT) domains target the non-receptor tyrosine kinases FAK and Pyk2 to cellular focal adhesion areas, where the signaling molecule paxillin is also located. Here, we report the crystal structures of the Pyk2 FAT domain alone or in complex with paxillin LD4 peptides. The overall structure of Pyk2-FAT is an antiparallel four-helix bundle with an up-down, up-down, right-handed topology. In the LD4-bound FAT complex, two paxillin LD4 peptides interact with two opposite sides of Pyk2-FAT, at the surfaces of the a1a4 and a2a3 helices of each FAT molecule. We also demonstrate that, while paxillin is phosphorylated by Pyk2, complex formation between Pyk2 and paxillin does not depend on Pyk2 tyrosine kinase activity. These experiments reveal the structural basis underlying the selectivity of paxillin LD4 binding to the Pyk2 FAT domain and provide insights about the molecular details which influence the different behavior of these two closely-related kinases.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 980114
• Report Number(s): BNL--93032-2010-JA
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 383; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
ADHESION
BEHAVIOR
CRYSTAL STRUCTURE
FATS
MOLECULES
PEPTIDES
PHOSPHOTRANSFERASES
SURFACES
TARGETS
TOPOLOGY
TYROSINE
national synchrotron light source