Figure 5.

The arginine-glutamate hasp of Gα. Switch (Swi) regions 1–3 in the crystal structure of α_t⋅GTP[γS] (3) are shown in relation to bound GTP (green; γ-phosphate colored red) and Mg²⁺ ion (magenta). Except for side chains of key amino acids, only main chains are depicted. The γ-phosphate of GTP (red) is linked to two amino acids (yellow, not labeled) in switch 1; these include R174 (on the left side of the picture) and T177. R174 corresponds to R201 of α_s, the target of ADP ribosylation by cholera toxin. T177 (T 204 in α_s) is linked to the γ-phosphate via bound Mg²⁺ (magenta). The γ-phosphate is linked to switch 2 by the main chain amide of G199 in α_t (red, not labeled; corresponding to G226 in α_s). The intramolecular hasp is the salt bridge between R204 (red; cognate to R231 in α_s) in switch 2 (the α2 helix) and E241 (blue; E268 of α_s) in α3. The hasp helps to maintain both the tight binding of GTP and the GTP-induced active conformation by fastening switch 2 and α3, thus reinforcing linkage of the glycine residue in switch 2 to the γ-phosphate of GTP.