Intramolecular dynamics within the N-Cap-SH3-SH2 regulatory unit of the c-Abl tyrosine kinase reveal targeting to the cellular membrane

Abstract

Background: c-Abl regulates cell signaling and participates in leukemia pathogenesis via Bcr-Abl chimeric protein. Results: N-Cap and SH3 residues acquire μs-ms motions within the regulatory unit and membrane anchoring upon protein activation. Conclusion: N-Cap-myristoyl tether triggers c-Abl to anchor membrane because of μs-ms dynamics within this regulatory region. Significance: Binding to the membrane is lost in Bcr-Abl chimeric protein, which underlies leukemia. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.