FIGURE 4.

Expected structural changes of ARA7 upon binding to VPS9a. a and b, the form B of Rab5A·GppNHp·Mg²⁺ (Protein Data Bank entry 1R2Q; green) and Rab5A·GDP·Co²⁺ (chain B of Protein Data Bank entry 1TU4; green), respectively, are superimposed on the structure of ARA7·GDP (magenta) bound to VPS9a (cyan). A subset of the VPS9a structure, including Asp¹⁸⁵ and Tyr²²⁵, whose side chains are drawn as ball-and-stick models, is displayed for clarity. Nucleotides in Rab5A and ARA7 are drawn as ball-and-stick models and colored in light green and pink, respectively. Structural differences between the switches and the phosphate-binding cassette are indicated by green-to-magenta arrows. The interswitch region of ARA7 is unzipped by hydrophobic contacts with VPS9a (Fig. 3), and the unzipping is represented by the Cα positions of the ARA7 Ala⁴⁵ and Rab5A Ala⁵⁵, indicated by orange spheres and an arrow. The side-chain oxygens of VPS9a and the oxygens coordinated to Co²⁺ (blue-gray sphere), or Mg²⁺ (gray sphere), of Rab5A are drawn as red spheres with red dots indicating coordination to the metal.