GPCRs are very dynamic (Fig. 2); they continuously diffuse through the plasma membrane and dimers (or oligomers) are continuously forming and falling apart. To simplify the analysis, we consider only dimerization. Dynamic dimerization equilibria exist that are characterized by a constant, rapidly fluctuating monomer and dimer fraction. Kasai et al. (2011) recently quantified the monomer-dimer equilibrium of the N-formyl peptide receptor (FPR), a GPCR. They found that: indicating that the dimer, denoted by m2, life-time is about 0.1 seconds (1/k−): 10 dimers fall apart every second. The total number of receptor monomers per cell, mT, was 6000. At thermodynamic equilibrium, when KD = m2/m2, and given mT = m + 2m2, the equilibrium concentrations of the monomer and the dimer become m = 3534 copies/cell and m2 = 1233 copies/cell: less than 50% of the monomers exist as dimers. The lifetime of a monomer equals 0.4 seconds (=kfm2/mT)−1. The diffusion coefficient of a monomer in the membrane sets the upper limit of the association rate constant (Shoup and Szabo, 1982) to 3 × 10−3 cell/copies (Lauffenburger and Linderman, 1993). The k+ of FPR is very close to this limit. Given a realistic diffusion coefficient (D) of 0.1 μm2/s for a GPCR (Hern et al., 2010), the average distance that a GPCR travels in a membrane in one second equals = 0.6 μm. |