Figure 2.

DEER distances of inactive and fully active β₂AR. See Figure S2 for raw DEER data.

(A) Distance distribution for carazolol-bound β₂AR. The dotted lines show simulated nitroxide spin label distance distributions for a state with a broken ionic lock using carazolol-bound β₂AR (PDB ID: 4GBR), and a state with an ionic lock intact using β₁AR (PDB ID: 2YCW) as shown in panels B and C.

(B) IA-PROXYL rotamers modeled onto β₂AR bound to carazolol (PDB ID: 4GBR) using MTSSLWizard. The distance between these possible rotamers is then determined in a pairwise manner to yield the predicted distance distribution shown in A.

(C) Similar analysis as in B was performed on the structure of β₁AR bound to carazolol but with an intact ionic lock. The red outline indicates rotamers modeled in B. The mean distance for a state with an intact ionic lock is predicted to be shorter than for β₂AR with a broken ionic lock.

(D) Distance distribution for β₂AR bound to BI167107 and Nb80. The dashed green line serves as a marker for the S4 state. The grey line represents the simulated distance distribution for β₂AR bound to BI167107 and Nb80 using the previously determined crystal structure (PDB ID: 3P0G) as shown in panel E.

(E) IA-PROXYL rotamer modeling of activated β₂AR bound to BI167107 and Nb80.