Trp-Trp acts as a multifunctional blocker for human bitter taste receptors, hTAS2R14, hTAS2R16, hTAS2R43, and hTAS2R46.

Many functional food ingredients activate human bitter taste receptors (hTAS2Rs). In this study, A novel inhibitor, Trp-Trp, for hTAS2R14 was identified by searching for the agonist peptide's analogs. Trp-Trp also inhibited hTAS2R16, hTAS2R43, and hTAS2R46, which share the same agonists with hTAS2R14. The multifunctional characteristic of Trp-Trp is advantageous for use as bitterness-masking agents in functional foods.

Enhancement of transcription efficiency by TAR-Tat system increases the functional expression of human olfactory receptors.

Humans have approximately 400 different olfactory receptors (hORs) and recognize odorants through the repertoire of hOR responses. Although the cell surface expression of hORs is critical to evaluate their response, hORs are poorly expressed on the surface of heterologous cells. To address this problem, previous studies have focused on hOR transportation to the membrane. Nevertheless, the response pattern of hORs to odorants has yet to be successfully linked, and the response sensitivity still remains to be improved. In this study, we demonstrate that increasing the transcriptional level can result in a significant increase in cell surface and functional expression of hORs. We used the TAR-Tat system, which increases the transcription efficiency through positive feedback, and found that OR1A1, OR6N2, and OR51M1 exhibited robust expression. Moreover, this system induces enhanced hOR responses to odorants, thus defining four hORs as novel n-hexanal receptors and n-hexanal is an inverse agonist to one of them. Our results suggested that using the TAR-Tat system and increasing the transcriptional level of hORs can help understanding the relationship between hORs and odorants that were previously undetectable. This finding could facilitate the understanding of the sense of smell by decoding the repertoire of hOR responses.

Engineered odorant receptors illuminate structural principles of odor discrimination.

A central challenge in olfaction is understanding how the olfactory system detects and distinguishes odorants with diverse physicochemical properties and molecular configurations. Vertebrate animals perceive odors via G protein-coupled odorant receptors (ORs). In humans, ~400 ORs enable the sense of smell. The OR family is composed of two major classes: Class I ORs are tuned to carboxylic acids while Class II ORs, representing the vast majority of the human repertoire, respond to a wide variety of odorants. How ORs recognize chemically diverse odorants remains poorly understood. A fundamental bottleneck is the inability to visualize odorant binding to ORs. Here, we uncover fundamental molecular properties of odorant-OR interactions by employing engineered ORs crafted using a consensus protein design strategy. Because such consensus ORs (consORs) are derived from the 17 major subfamilies of human ORs, they provide a template for modeling individual native ORs with high sequence and structural homology. The biochemical tractability of consORs enabled four cryoEM structures of distinct consORs with unique ligand recognition properties. The structure of a Class I consOR, consOR51, showed high structural similarity to the native human receptor OR51E2 and yielded a homology model of a related member of the human OR51 family with high predictive power. Structures of three Class II consORs revealed distinct modes of odorant-binding and activation mechanisms between Class I and Class II ORs. Thus, the structures of consORs lay the groundwork for understanding molecular recognition of odorants by the OR superfamily.

Impact of Quorum Sensing Molecules on Plant Growth and Immune System.

Bacterial quorum-sensing (QS) molecules are one of the primary means allowing communication between bacterial cells or populations. Plants also evolved to perceive and respond to those molecules. N-acyl homoserine lactones (AHL) are QS molecules, of which impact has been extensively studied in different plants. Most studies, however, assessed the interactions in a bilateral manner, a nature of interactions, which occurs rarely, if at all, in nature. Here, we investigated how Arabidopsis thaliana responds to the presence of different single AHL molecules and their combinations. We assumed that this reflects the situation in the rhizosphere more accurately than the presence of a single AHL molecule. In order to assess those effects, we monitored the plant growth and defense responses as well as resistance to the plant pathogen Pseudomonas syringae pathovar tomato (Pst). Our results indicate that the complex interactions between multiple AHL and plants may have surprisingly similar outcomes. Individually, some of the AHL molecules positively influenced plant growth, while others induced the already known AHL-priming for induced resistance. Their combinations had a relatively low impact on the growth but seemed to induce resistance mechanisms. Very striking was the fact that all triple, the quadruple as well as the double combination(s) with long-chained AHL molecules increased the resistance to Pst. These findings indicate that induced resistance against plant pathogens could be one of the major outcomes of an AHL perception. Taken together, we present here the first study on how plants respond to the complexity of bacterial quorum sensing.