Structure of neurofibromin-GRD domain (NF1-333) in a ribbon representation. The central domain (NF1c) is shown in light blue, green, yellow, and brown and the extra domain (NF1ex) in dark blue and red. Regions that are not visible in the neurofibromin-GRD model were complemented by the corresponding segments derived from the GAP-334 model and are shown as dotted lines. Helices α6c and α7c, forming the bottom of the Ras-binding groove, are indicated. The variable loop (L6c) and α2c helix, involved in the interaction with Ras, and finger loop (L1c), which provides an Arg residue (R1276) to the active site of Ras to stabilize the transition state of the GTPase reaction, are also indicated.