Figure 7.

Ubiquitination of Lys-1155 and Lys-1230 in the GRD of IQGAP1 would impair CDC42 binding. A, two CDC42 molecules (green with red switch regions) bind to the GRD (yellow). One CDC42 molecule binds to the extra subdomain (Ex mode binding), whereas the other CDC42 molecule binds the middle region of GRD (RasGAP mode binding). B, ubiquitin (orange) conjugation at Lys-1155 tethers a large molecule very close to the CDC42 Ex mode-binding site; shown here occupied by CDC42. Inset, a magnified view of the interaction, with Gly-75 and Gly-76 of ubiquitin shown in stick representation. C, conjugation of ubiquitin at Lys-1230 within the GRD of IQGAP1. D, the same orientation of the GRD with CDC42 occupying the RasGAP-binding site. E, significant steric overlap would prevent simultaneous ubiquitin conjugation and CDC42 binding to the GRD.