Receptor Allosterism Governs the Coding of Configurational Walnut Aroma

Abstract Walnut aroma is a configurational odor identity, primarily attributed to a walnut-typical 1:1 concentration ratio of the key food odorants (KFO) (2E,4E,6Z)-nona-2,4,6-trienal and 3-hydroxy-4,5-dimethylfuran-2(5H)-one (sotolon), which by themselves impart oatmeal- and fenugreek-like odor notes, respectively. OR8D1 has been identified as a sotolon-responsive receptor, recently. A receptor for (2E,4E,6Z)-nona-2,4,6-trienal was unknown. We screened a collection of 766 odorant receptor variants with (2E,4E,6Z)-nona-2,4,6-trienal, and OR2J2 solely emerged as a responder. Testing OR2J2 with 190 KFOs and series of aldehydes revealed its KFO-biased, aldehyde-centered, and EC50-ranked spectrum of 47 agonists, with (2E,4E,6Z)-nona-2,4,6-trienal as the most potent and efficient agonist. Concentration–response relationships of (2E,4E,6Z)-nona-2,4,6-trienal, sotolon, and their 1:1 mixtures on OR2J2 and OR8D1 demonstrated (2E,4E,6Z)-nona-2,4,6-trienal as negative allosteric modulator significantly attenuating the efficacy of sotolon at OR8D1. In summary, our findings show that configurational walnut aroma is orthosterically and allosterically encoded, demonstrating yet another way odorants interact at receptors to produce novel response patterns.