Figure 4.

Structures of Gα_12/13 subunits in activated and deactivated states. (A) The activated Gα_i/12·GDP·AlF₄⁻ complex. The region of the αB-αC loop distinct from that of Gα_i/13 is colored purple. The three conformationally flexible “switch regions” of the Gα subunit are red and labeled with Roman numerals (I–III). A fourth, apparently Gα_12/13-specific element (the “spring”) is likewise colored red. The Mg²⁺·GDP·AlF₄⁻ ligand complex is shown as a ball-and-stick model, with carbons colored gray, oxygens red, nitrogens blue, phosphates yellow, fluorines purple, aluminum cyan and magnesium black. Waters are shown as red spheres. (B) The deactivated Gα_i/13·GDP complex adopts an unusually open conformation in which the α-helical domain has rotated ~8.5° away from the Ras-like domain. Switch II is almost completely disordered, and switch III has rotated away (up in the figure) from the nucleotide binding site. (C) Stereo view of the C^α traces of Gα_i/12·GDP·AlF₄⁻ (green with red switch regions) and Gα_i/13·GDP (black with yellow switch regions), superimposed using their Ras-like domains. The glutamate side chain in the “spring” of each α-helical domain (E175 in Gα₁₂, E172 in Gα₁₃) is shown as a stick model.