Structure-Based Sequence Alignment of the Transmembrane Domains of All Human GPCRs: Phylogenetic, Structural and Functional Implications
Fig 8
Native activation “hot-spot” residues (NACHOs), which are contacts that change upon receptor activation.
The width of the green lines is proportional to the number of contacts common to all six structures (RHO, β2AR, M2, and their active structures). Blue shows the contacts present only in inactive structures, and not in inactive structures; while red shows the opposite. The upper diagrams show contacts in the extracellular half of the membrane. We see that there is no systematic change common to the class A receptors in the conformation of the extracellular half of the TMs. This is not obvious, because there are conformational changes accompanying ligand binding. All the systematic changes, which enable G protein binding, occur in the intracellular half of the TMs. The list only contains 15 different residues in 15 different contacts. Thus many of the residues switch partners upon activation.