Crystal structure of the N-terminal SH3 domain of mouse βPIX, p21-activated kinase-interacting exchange factor

The mouse βPIX–SH3 domain, residues 8–63 of P21-activated kinase interacting exchange factor, has been characterized by X-ray diffraction. Crystals belonging to space group P3221 diffracted to 2.0 Å and the structure was phased by the single-wavelength anomalous diffraction method. The domain is a compact β-barrel with an overall conformation similar to the general SH3 structure. The X-ray structure shows mouse βPIX–SH3 domain binding the way in which the βPIX characteristic amino acids do so for an unconventional ligand binding surface. This arrangement provides a rationale for the unusual ligand recognition motif exhibited by mouse βPIX–SH3 domain. Comparison with another SH3/peptide complex shows that the recognition mode of the mouse βPIX–SH3 domain should be very similar to the RXXK ligand binding mode. The unique large and planar hydrophobic pocket may contribute to the promiscuity of βPIX–SH3 domain resulting in its multiple biological functions.