FIGURE 1.

Domain organization of Abl kinases and crystal structure of the down-regulated c-Abl core. Upper, the c-Abl-1b protein kinase consists of a myristoylated (Myr) N-cap region, followed by SH3 and SH2 domains, the SH2/kinase linker, the tyrosine kinase domain, and a long last exon region with a C-terminal actin-binding domain (ABD). In Bcr-Abl, N-terminal fusion to Bcr sequences removes most of the N-cap, leaving the remainder of Abl intact. The Bcr-derived portion includes an N-terminal coiled-coil (CC) oligomerization domain as well as Dbl and pleckstrin homology domains (DH/PH). Lower, the x-ray crystal structure of the c-Abl-1b core protein in the down-regulated state (PDB code 2FO0) is rendered as a ribbon (lower left) and with the surface added (right) to emphasize the tight molecular packing of the regulatory regions (N-cap/SH3/SH2/linker) against the kinase domain. The unstructured portion of the myristoylated N-cap that engages the C-lobe of the kinase domain is shown as a dotted line. Domains in the structure are color-coded and correspond to the schematic shown at the top. In the kinase domain, the positions of helix αC and the activation loop (Act. Loop) are rendered in cyan and magenta, respectively. The side chain of the activation loop autophosphorylation site (Tyr⁴¹²) is also shown.