Interactions involving H139Ran, Y98Ran, and Ran's basic patch switching mechanism. See text for details. This figure focuses on three structural forms: (A,D) canine Ran-GDP (pdb code: 1BYU), (B,E) human Ran in complex with RCC1 (pdb code: 1I2M), and (C) human Ran in complex with importin-β and a GTP analog (pdb code: 1IBR). The perspective forA–C is as that for Sec4p in Figure 4 B; the perspective for D,E is rotated approximately 180° relative to that for A,B. The reaction pathway for these three forms of Ran is shown between the upper and lower figures. Note that in C the invariant histidine at position 139 in Ran forms both an aromatic-aromatic interaction and an NH-π (or perhaps a CH-π) interaction with Trp342 of importin-β. (F) Proposed mechanism for Ran nucleotide exchange. The conformation of Canine Ran-GDP is shown with arrows indicating the direction of movement of key residues and main-chain regions upon binding to RCC1. A movie demonstrating the conformational changes involved in this mechanism is available as supplementary information at www.genome.org.
