This content will become publicly available on June 13, 2024
- NSF-PAR ID:
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- Journal Name:
- Proceedings of the National Academy of Sciences
- Medium: X
- Sponsoring Org:
- National Science Foundation
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The biological membrane is an efficient barrier against water-soluble substances. Solute transporters circumvent this membrane barrier by transporting water-soluble solutes across the membrane to the other sides. These transport proteins are thus required for all living organisms. Microorganisms, such as bacteria, effectively exploit solute transporters to acquire useful nutrients for growth or to expel substances that are inhibitory to their growth. Overall, there are distinct types of related solute transporters that are grouped into families or superfamilies. Of these various transporters, the major facilitator superfamily (MFS) represents a very large and constantly growing group and are driven by solute- and ion-gradients, making them passive and secondary active transporters, respectively. Members of the major facilitator superfamily transport an extreme variety of structurally different substrates such as antimicrobial agents, amino acids, sugars, intermediary metabolites, ions, and other small molecules. Importantly, bacteria, especially pathogenic ones, have evolved multidrug efflux pumps which belong to the major facilitator superfamily. Furthermore, members of this important superfamily share similar primary sequences in the form of highly conserved sequence motifs that confer useful functional properties during transport. The transporters of the superfamily also share similarities in secondary structures, such as possessing 12- or 14-membrane spanning α-helices and the more recently described 3-helix structure repeat element, known as the MFS fold. The three-dimensional structures of bacterial multidrug efflux pumps have been determined for only a few members of the superfamily, all drug pumps of which are surprisingly from Escherichia coli. This review briefly summarizes the structural properties of the bacterial multidrug efflux pumps of the major facilitator superfamily in a comparative manner and provides future directions for study.more » « less
Seed development largely depends on the long‐distance transport of sucrose from photosynthetically active source leaves to seed sinks. This source‐to‐sink carbon allocation occurs in the phloem and requires the loading of sucrose into the leaf phloem and, at the sink end, its import into the growing embryo. Both tasks are achieved through the function of
SUTsucrose transporters. In this study, we used vegetable peas ( Pisum sativumL.), harvested for human consumption as immature seeds, as our model crop and simultaneously overexpressed the endogenous transporter in the leaf phloem and in cotyledon epidermal cells where import into the embryo occurs. Using this ‘Push‐and‐Pull’ approach, the transgenic SUT1 plants displayed increased sucrose phloem loading and carbon movement from source to sink causing higher sucrose levels in developing pea seeds. The enhanced sucrose partitioning further led to improved photosynthesis rates, increased leaf nitrogen assimilation, and enhanced source‐to‐sink transport of amino acids. Embryo loading with amino acids was also increased in SUT1 ‐overexpressors resulting in higher protein levels in immature seeds. Further, transgenic plants grown until desiccation produced more seed protein and starch, as well as higher seed yields than the wild‐type plants. Together, the results demonstrate that the SUT1 ‐overexpressing plants with enhanced sucrose allocation to sinks adjust leaf carbon and nitrogen metabolism, and amino acid partitioning in order to accommodate the increased assimilate demand of growing seeds. We further provide evidence that the combined Push SUT1 ‐and‐Pull approach for enhancing carbon transport is a successful strategy for improving seed yields and nutritional quality in legumes.
In contrast to an obsolete notion that erythrocytes, or red blood cells (
RBCs), play a passive and minor role in haemostasis and thrombosis, over the past decades there has been increasing evidence that RBCs have biologically and clinically important functions in blood clotting and its disorders. This review summarizes the main mechanisms that underlie the involvement of RBCs in haemostasis and thrombosis in vivo, such as rheological effects on blood viscosity and platelet margination, aggregation and deformability of RBCs; direct adhesion and indirect biochemical interactions with endothelial cells and platelets. The ability of stored and pathologically altered RBCs to generate thrombin through exposure of phosphatidylserine has been emphasized. The procoagulant and prothrombotic potential of RBC‐derived microparticles transfused with stored RBCs or formed in various pathological conditions associated with haemolysis has been described along with prothrombotic effects of free haemoglobin and haem. Binding of fibrinogen or fibrin to RBCs may influence their effects on fibrin network structure, clot mechanical properties and fibrinolytic resistance. Recent data on platelet‐driven clot contraction show that RBCs compressed by platelets pulling on fibrin form a tightly packed array of polyhedral erythrocytes, or polyhedrocytes, which comprises a nearly impermeable barrier important for haemostasis and wound healing. RBCs may perform dual roles, both helping to stem bleeding but at the same time contributing to thrombosis in a variety of ways.
Membrane‐embedded transporters impart essential functions to cells as they mediate sensing and the uptake and extrusion of nutrients, waste products, and effector molecules. Promiscuous multidrug exporters are implicated in resistance to drugs and antibiotics and are highly relevant for microbial engineers who seek to enhance the tolerance of cell factory strains to hydrophobic bioproducts. Here, we report on the identification of small multidrug resistance (SMR) transporters in early‐branching anaerobic fungi (Neocallimastigomycetes). The SMR class of transporters is commonly found in bacteria but has not previously been reported in eukaryotes. In this study, we show that SMR transporters from anaerobic fungi can be produced heterologously in the model yeast
Saccharomyces cerevisiae, demonstrating the potential of these proteins as targets for further characterization. The discovery of these novel anaerobic fungal SMR transporters offers a promising path forward to enhance bioproduction from engineered microbial strains.
Marine bacterioplankton face stiff competition for limited nutrient resources. SAR11, a ubiquitous clade of very small and highly abundant Alphaproteobacteria, are known to devote much of their energy to synthesizing ATP-binding cassette periplasmic proteins that bind substrates. We hypothesized that their small size and relatively large periplasmic space might enable them to outcompete other bacterioplankton for nutrients. Using uptake experiments with 14C-glycine betaine, we discovered that two strains of SAR11, Candidatus Pelagibacter sp. HTCC7211 and Cand. P. ubique HTCC1062, have extraordinarily high affinity for glycine betaine (GBT), with half-saturation (Ks) values around 1 nM and specific affinity values between 8 and 14 L mg cell−1 h−1. Competitive inhibition studies indicated that the GBT transporters in these strains are multifunctional, transporting multiple substrates in addition to GBT. Both strains could use most of the transported compounds for metabolism and ATP production. Our findings indicate that Pelagibacter cells are primarily responsible for the high affinity and multifunctional GBT uptake systems observed in seawater. Maximization of whole-cell affinities may enable these organisms to compete effectively for nutrients during periods when the gross transport capacity of the heterotrophic plankton community exceeds the supply, depressing ambient concentrations.more » « less