Fig 1.
The minimal kinetic model for the odor response.
a. A schematic of olfactory signaling cascades. Golf, olfactory G-protein binding to and the subsequent release of GαGTP subunit from the receptor via GDP/GTP exchange () elicit downstream signal cascades: production of second messengers (cAMP) via stimulation of adnenylyl cyclase III, followed by depolarization of membrane potential via cAMP-induced opening of ion-channels [39, 40]. The downstream signal is stronger (the thicker arrow in purple) when odorant is bound to the OR. b. The four-parameter model (Eq 3) to describe the dose-response data.
Fig 2.
Analysis of dose-response data for odorant-OR pairs.
Examples of fit using Eq 3 are shown for some odorant-receptor pairs: a. allyl phenylacetate−OR51L1 (B = 2.18, δSmax = 4.76, log10 K1/2 = −7.56, H = 0.7); b. androstenone−OR7D4 (B = 0.21, δSmax = 3.09, log10 K1/2 = −5.72, H = 1.4); c. geranyl acetate−OR14A16 Indel (B = 0.32, δSmax = 0.96, log10 K1/2 = −3.84, H = 6.6); d. eugenol−OR10G7 (B = 3.69, δSmax = 5.21, log10 K1/2 = −8.95, H = 0.3). e. Dose-response data for 22 odorant-OR pairs collapsed onto a universal curve, f = 10ξ/(1 + 10ξ), where f = δS/δSmax and ξ = Hlog10(CO/K1/2) (orange line). For clarity, only the data from 22 activating pairs are presented.
Fig 3.
Distribution of effective odorant concentration for the activation of partner receptors.
a. Histogram of EC50 calculated for all dose-response data (gray). Among the 535 interacting odorant-receptor pairs, 475 pairs exhibit activation (δSmax > 0, red), and the remaining pairs show deactivation (δSmax < 0, cyan). Note that the red and cyan distributions sum to make the gray (all pairs) distribution. The EC50 values for the pairs exhibiting activation can be fitted effectively to a Gaussian [42] with μc = −3.6 and σc = 1.1; for all pairs, μc = −4.0 and σc = 1.8. The skewness of the distribution is likely to be contributed from the extremal (cutoff-based) nature of the measurement, which unavoidably eliminates the weakly interacting (high EC50) pairs from the data. The deactivating pairs are characterized with a broader distribution of EC50 values. The super-strong binders (EC50 < −9) are exclusively contributed by those among the odorant-receptor pairs demonstrating the deactivation. b. Odorant-specific differential response for the top five broadly-interacting odorants.
Fig 4.
Distributions of efficacy and Hill coefficient.
a. Probability density of efficacy ρ(E) and b. the histogram of Hill coefficient for the ensemble of all interacting odorant-OR pairs. ρ(E) was fitted to a sum of two exponentials (Eq 8).
Fig 5.
Analysis of the top five broadly-interacting odorants.
a. Fits of efficacy (E) versus basal activity data (B) for distinct odorants (λ) using Eq 10. The name of each odorant is provided with the number of responding receptors inside the parenthesis. b. Distributions of ω for the five broadly-interacting odorants.
Table 1.
OR averaged parameters determined for the top five broadly-interacting odorants.