Fig. 2. Identification of PTH1R-arr2 intermolecular pairs of proximal residues via thiol trapping.

a Nucleophilic substitution reaction between the Cys thiol and the haloalkane moiety of BrEtY. The reaction occurs only when the two moieties are close to each other, and yields a stable thioether. b The length of BrEtY crosslink (10.2 Å) was estimated as the maximal distance between Cβ atoms in the BrEtY-cysteine adduct based on the extensive conformational sampling of the adduct molecule. c–e Crosslinking matrix for Cys-PTH1R positions (row) with BrEtY-arr2 positions (column). Fields are colored according to the crosslinking yield of all combinations yielding significant signal over background noise (n ≥ 3, see Supplementary Data 2). Gray squares indicate crosslinking signals not significantly different from control background noise, white indicate combinations that were not tested. All tested combinations are shown in Supplementary Figs. 6, 7.