The sesquiterpene abscisic acid (ABA) is an ancient stress response molecule. In plants, many ABA-dependent processes operate via PYR/PYL/RCAR receptor complexes, but results from several studies have suggested that not all plant responses function through this mechanism. Since the ABA-dependent processes of animals and humans also operate in the absence of such receptors, we hypothesize that plant and animal proteomes harbour proteins with undiscovered ABA-binding sites. We propose that carefully curated amino acid search motifs deduced from the binding sites of experimentally confirmed ABA-binding proteins can identify many more candidates in plant and animal proteomes. Some of these candidates show structural folds that are compatible with ABA-binding. This approach identifies plant candidates including annotated ABA downstream signaling components SnRK2.2 and SnRK2.6, and proteins involved in protein folding and RNA polyadenylation. The identified ABA-binding candidates in the human proteome affect among other processes, immune responses and tumor progression. If these candidates are eventually validated experimentally, it will imply that the regulation and tuning of ABA-dependent processes is considerably more complex than hitherto suspected. It will also help to clarify the role of this conserved signaling molecule in mammals.

Abscisic acid (ABA) is a “classical” plant hormone and is key to many plant responses, notably seed germination, transpiration and defence. It is becoming increasingly clear that ABA acts not just through the canonical PYL/PYR/RCAR receptors but also through other proteins that can interact specifically with ABA. Here we use genomic and transcriptomic resources to show that the human proteome also contains proteins with specific ABA-binding signatures and that some of these potential ABA-binding proteins may have roles in cancer and diabetes. In addition, there is evidence for the presence of ABA in humans; however, the source of it remains somewhat inconclusive. Here we propose an ABA synthesis pathway that, much like in fungi, does not include carotenoids but proceeds via farnesyl pyrophosphate. In summary, we review the current status of ABA research in Homo sapiens and propose avenues that might lead to novel insights into the synthesis and biological roles of this ancient hormone, e.g., in obesity and inflammation.

Nitric oxide (NO) is a universal and ancient signaling molecule that modulates a myriad of biological processes in various organisms. In animals, NO interacts with and activates the guanylate cyclase at an allosteric heme-binding site, causing an elevation of the second messenger cGMP, resulting in vasodilation. In plants, this heme-based sensing of NO appears to be elusive despite NO being associated with broad plant processes including the growth, re-orientation and ovule targeting of pollen tubes. Here, we report the identification of an ORGANELLAR EXONUCLEASE, OEX1, as a novel hemoprotein, and show that pollen tubes of oex1 mutant plants have markedly reduced sensitivity to NO. Spectroscopic data show that OEX1 generates Soret peak diagnostic of heme interaction, which can be oxidized, reduced and NO-ligated accordingly. Importantly, substitution of key amino acids at the heme-interacting site lowers the Soret signatures indicating reduced heme and concomitantly also NO interactions. Furthermore, comparative genomics reveals NO-dependent molecular functions and biological processes that are affected by OEX1 thereby linking heme-sensing of NO to responses at the systems level. As a fast-diffusible gaseous signaling molecule, the molecular perception is crucial for the maintenance of cellular homeostasis under changing environmental conditions, thus the extension of heme-based gas sensing studies to crops could enhance the effectiveness of NO application in horticulture.

Growing evidence suggests that plant proteomes contain numerous proteins that specifically bind abscisic acid (ABA). Many of them are complex multidomain proteins where specific ABA-binding can cause biochemical and physiological changes. Here we show that the Arabidopsis thaliana K ⁺ transporter AtKUP5 contains both a functional cytoplasmic N-terminal adenylate cyclase (AC) enabling the synthesis of 3’,5’-cAMP from ATP and a C-terminal phosphodiesterase (PDE) that hydrolyses 3’,5’-cAMP to 5’-AMP. We found that ABA binds in a ligand-specific manner to the catalytic center of the PDE thereby causing a reduction of 3’,5’-cAMP hydrolysis in vitro . The hydrolytic activity of the PDE is ABA concentration-dependent, biphasic and requires the presence of an intact ABA-binding site similar to the one in the canonical Pyrabactin resistance 1/PYR-like/Abscisic acid receptors, with V _max of 1.19 pmole min□ ¹ μg□ ¹ in the absence of ABA, increasing to 1.58 pmole min□ ¹ μg□ ¹ at 2 nM ABA, and decreasing to 0.75 pmole min□ ¹ μg□ ¹ at 50 nM ABA. These findings are therefore consistent with a direct role of ABA in PDE activity modulations and form a functional link between 3’,5’-cAMP signaling and K ⁺ flux. Furthermore, we predict that a growing number of such receptor-like proteins that specifically and directly interact with ABA will be discovered thereby uncovering complex and ancient layers of signaling and metabolic regulation.