Structural and Mechanistic Insights into the Interaction between Pyk2 and Paxillin LD Motifs |
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| Institution: | 1. Department of Structural Biology, St. Jude Children''s Research Hospital, Memphis, TN 38105, USA;2. Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children''s Research Hospital, Memphis, TN 38105, USA;1. Departments of Biophysics and Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9050, USA;2. Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9050, USA;1. Waksman Institute of Microbiology, Rutgers, The State University of New Jersey, NJ 08854, USA;2. Rowan University School of Osteopathic Medicine, Stratford, NJ 08084, USA;3. Public Health Research Institute Center, New Jersey Medical School, Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey, NJ 07103, USA;4. Department of Biochemistry and Molecular Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA;5. Institutes of Gene Biology and Molecular Genetics, Russian Academy of Sciences, Leninsky Avenue, 14, 119991 Moscow, Russia;1. Department of Physics, University of California at San Diego, La Jolla, CA 92093, USA;2. Department of NanoEngineering, University of California at San Diego, La Jolla, CA 92093, USA;1. Department of Molecular Biology, University of Bergen, Postbox 7803, 5020 Bergen, Norway;2. Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom;3. Centre for Applied Biotechnology, Uni Research, Postbox 7810, 5020 Bergen, Norway;4. Faculty of Medicine and Dentistry, University of Bergen, Haukelandsveien 28, 5020 Bergen, Norway;5. Institute of Molecular Biotechnology (IMBA), Dr. Bohr-Gasse 3, 1030 Vienna, Austria |
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| 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 (paxillin133 -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. |
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