Supplemental Data for 'Signaling bias of the protease-activated receptor-1 is dictated by distinct GRK5 and β-arrestin-2 determinants'

The dataset contains 7 ensembles of structural models of unactivated, thrombin-activated, and APC-activated PAR1 with and without intracellular effectors. To gain insight into the conformational preferences of unactivated PAR1, thrombin-activated PAR1, and APC-activated PAR1, we built an ensemble of 100 structural models of each of these molecular species using AlphaFold 3 (AF3). To investigate the structural basis of favorable core-mediated coupling between βarr2 and APC-activated but not Th-activated PAR1, we constructed 100 models of βarr2 complexes with Th-activated PAR1 with distal C-terminus phosphorylated, and APC-activated PAR1 with both distal and proximal C-terminus phosphorylated. Our results are consistent with Th-activated but not APC-activated PAR1 forming multimeric complexes that simultaneously include a core-engaged heterotrimeric G protein and a tail-hanging βarr2. To reveal the structural basis for such complexes, we generated 100 models of either thrombin- or APC-activated PAR1 with different phospho-sites in complex with both Gq and βarr2 using AF3.