Fig. 8: Evaluation of OR dimer and MOR-DOR hetero-trimer formation across expression levels.
Snapshot of OR distributions as monomers, homodimers, and heterodimers at selected low physiological concentrations (number densities) in the PM expressing KOR, MOR, and DOR at a 1:1:1 ratio by simulation (a, b), and estimation of the number of heterotrimers (2 DOR and 1 MOR or 1 DOR and 2 MOR molecules) in cells co-expressing various concentrations of DOR and MOR at a 1:1 ratio calculated by using koff and kon evaluated in these studies (c, d). a Schematic figure showing the kinetic parameters obtained in this work at the steady state (left) and after DAMGO stimulation (right). b Simulated distributions of ORs expressed at 1 (left) and 10 (right) copies/µm2. Note that the area sizes are different (100 and 10 µm2 for 1 and 10 copies/µm2, respectively) to match the total copy number to 100 in each box. For the detailed mathematical model, see Supplementary Note 1. c Schematic diagram of trimer formation for MOR and DOR under conditions with the absence of interference between the homodimer and heterodimer formation sites, using the kinetic parameters of homo- and hetero-interactions of MOR and DOR obtained in these studies. For the details of conditions and calculations, see Supplementary Note 1. d Estimated fractions of monomers (M + D), dimers (MM + DD + DM), and trimers (DMM + DDM) in terms of the total numbers of protomers.
