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The barley Mla locus contains functionally diversified genes that encode intracellular nucleotide-binding leucine-rich repeat receptors (NLRs) and confer strain-specific immunity to biotrophic and hemibiotrophic fungal pathogens. In this study, we isolated a barley gene Scs6, which is an allelic variant of Mla genes but confers susceptibility to the isolate ND90Pr (Bs ND90Pr ) of the necrotrophic fungus Bipolaris sorokiniana. We generated Scs6 transgenic barley lines and showed that Scs6 is sufficient to confer susceptibility to Bs ND90Pr in barley genotypes naturally lacking the receptor. The Scs6-encoded NLR (SCS6) is activated by a nonribosomal peptide (NRP) effector produced by Bs ND90Pr to induce cell death in barley and Nicotiana benthamiana. Domain swaps between MLAs and SCS6 reveal that the SCS6 leucine-rich repeat domain is a specificity determinant for receptor activation by the NRP effector. Scs6 is maintained in both wild and domesticated barley populations. Our phylogenetic analysis suggests that Scs6 is a Hordeum-specific innovation. We infer that SCS6 is a bona fide immune receptor that is likely directly activated by the nonribosomal peptide effector of Bs ND90Pr for disease susceptibility in barley. Our study provides a stepping stone for the future development of synthetic NLR receptors in crops that are less vulnerable to modification by necrotrophic pathogens., (© 2024 The Author(s). New Phytologist © 2024 New Phytologist Foundation. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

In Escherichia coli, the master transcription regulator catabolite repressor activator (Cra) regulates >100 genes in central metabolism. Cra binding to DNA is allosterically regulated by binding to fructose-1-phosphate (F-1-P), but the only documented source of F-1-P is from the concurrent import and phosphorylation of exogenous fructose. Thus, many have proposed that fructose-1,6-bisphosphate (F-1,6-BP) is also a physiological regulatory ligand. However, the role of F-1,6-BP has been widely debated. Here, we report that the E. coli enzyme fructose-1-kinase (FruK) can carry out its "reverse" reaction under physiological substrate concentrations to generate F-1-P from F-1,6-BP. We further show that FruK directly binds Cra with nanomolar affinity and forms higher order, heterocomplexes. Growth assays with a ΔfruK strain and fruK complementation show that FruK has a broader role in metabolism than fructose catabolism. Since fruK itself is repressed by Cra, these newly-reported events add layers to the dynamic regulation of E. coli's central metabolism that occur in response to changing nutrients. These findings might have wide-spread relevance to other γ-proteobacteria, which conserve both Cra and FruK., Competing Interests: Conflict of interests During the course of this work, Dr Bose served on the Scientific Advisory Board and was a consultant for Azitra, Inc and Merck & Co, Inc. These activities did not financially support and are unrelated to the current manuscript. The other authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In Escherichia coli , the master transcription regulator Catabolite Repressor Activator (Cra) regulates >100 genes in central metabolism. Cra binding to DNA is allosterically regulated by binding to fructose-1-phosphate (F-1-P), but the only documented source of F-1-P is from the concurrent import and phosphorylation of exogenous fructose. Thus, many have proposed that fructose-1,6-bisphosphate (F-1,6-BP) is also a physiological regulatory ligand. However, the role of F-1,6-BP has been widely debated. Here, we report that the E. coli enzyme fructose-1-kinase (FruK) can carry out its "reverse" reaction under physiological substrate concentrations to generate F-1-P from F-1,6-BP. We further show that FruK directly binds Cra with nanomolar affinity and forms higher order, heterocomplexes. Growth assays with a Δ fruK strain and fruK complementation show that FruK has a broader role in metabolism than fructose catabolism. The Δ fruK strain also alters biofilm formation. Since fruK itself is repressed by Cra, these newly-reported events add layers to the dynamic regulation of E. coli central metabolism that occur in response to changing nutrients. These findings might have wide-spread relevance to other γ-proteobacteria, which conserve both Cra and FruK., Competing Interests: Conflict of Interests. During the course of this work, Dr. Bose served on the Scientific Advisory Board and was a consultant for Azitra, Inc and Merck & Co, Inc. These activities did not financially support and are unrelated to the current manuscript. The other authors declare no conflict of interest.

We study the lateral domain structure in a coarse-grained molecular model for multicomponent lipid bilayers by semi-grandcanonical Monte Carlo simulations. The membranes are filled with liquid ordered (lo) domains surrounded by a liquid disordered (ld) matrix. Depending on the membrane composition and temperature, we identify different morphological regimes: one regime (I) where the lo domains are small and relatively compact, and two regimes (II, II') where they are larger and often interconnected. In the latter two regimes, the ld matrix forms a network of disordered trenches separating the lo domains, with a relatively high content of interdigitated line defects. Since such defects are also a structural element of the modulated ripple phase in one component membranes, we argue that the regimes II, II' may be amorphous equivalents of the ripple phase in multicomponent membranes. We also analyze the local structure and provide evidence that the domains in regime I are stabilized by a monolayer curvature mechanism postulated in earlier work [S. Meinhardt et al., PNAS, 2013, 110, 4476].