Conformational transitions for “activation” of Gαs proteins.

The video displays the different transitions (morph between structures) that Gαs undergoes when moving from the inactive GDP-bound state (PDB: 6EG8) to the G₀ state (guanine nucleotide free) induced by binding to selected activated class A or class B GPCRs. Transition 1: inactive to CCK1R-bound. Transition 2: inactive to β2-AR-bound. Transition 3: β2-AR-bound to CCK1R-bound. Transition 4: inactive to GLP-1R-bound to CCK1R-bound. Transition 5: inactive to EP4R-bound to CCK1R-bound. The protein backbone is displayed in ribbon format with the carboxyl-terminal residues of the αH5 shown also in stick format (coloured by heteroatom). Gs-GDP (grey; PDB: 6EG8), CCK1R-bound (gold), β2-AR-bound (blue; PDB: 3SN6), GLP-1R-bound (green; PDB:6X18), EP4R-bound (red; PDB: 7D7M). The αH5 has a “hook” conformation in the inactive G protein, and this conformation is maintained in most active state structures. In contrast, the far carboxyl-terminal residues of the αH5 unwinds to enable binding to the CCK1R. Unwinding of the α-5 helix is also seen with the EP4R complex, but this is accommodated by projection of the carboxyl-terminal amino acid side chains between the base of TM7 and TM1 (see Fig 4J). αH5, α5 helix; CCK, cholecystokinin; CCK1R, cholecystokinin type 1 receptor; GPCR, G protein–coupled receptor.

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