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Journal of Experimental Botany Sep 2023The ureides allantoin and allantoate serve as nitrogen (N) transport compounds in plants, and more recently, allantoin has been shown to play a role in signaling. In...
The ureides allantoin and allantoate serve as nitrogen (N) transport compounds in plants, and more recently, allantoin has been shown to play a role in signaling. In planta, tissue ureide levels are controlled by the activity of enzymes of the purine degradation pathway and by ureide transporters called ureide permeases (UPS). Little is known about the physiological function of UPS proteins in crop plants, and especially in monocotyledon species. Here, we identified 13 TaUPS genes in the wheat (Triticum aestivum L.) genome. Phylogenetic and genome location analyses revealed a close relationship of wheat UPSs to orthologues in other grasses and a division into TaUPS1, TaUPS2.1, and TaUPS2.2 groups, each consisting of three homeologs, with a total of four tandem duplications. Expression, localization, and biochemical analyses resolved spatio-temporal expression patterns of TaUPS genes, transporter localization at the plasma membrane, and a role for TaUPS2.1 proteins in cellular import of ureides and phloem and seed loading. In addition, positive correlations between TaUPS1 and TaUPS2.1 transcripts and ureide levels were found. Together the data support that TaUPSs function in regulating ureide pools at source and sink, along with source-to-sink transport. Moreover, comparative studies between wheat cultivars grown at low and high N strengthened a role for TaUPS1 and TaUPS2.1 transporters in efficient N use and in controlling primary metabolism. Co-expression, protein-protein interaction, and haplotype analyses further support TaUPS involvement in N partitioning, N use efficiency, and domestication. Overall, this work provides a new understanding on UPS transporters in grasses as well as insights for breeding resilient wheat varieties with improved N use efficiency.
Topics: Allantoin; Membrane Transport Proteins; Triticum; Nitrogen; Phylogeny; Plant Breeding
PubMed: 37478311
DOI: 10.1093/jxb/erad286 -
The Journal of General Physiology Jul 2019The lactose permease (LacY) of is the prototype of the major facilitator superfamily, one of the largest families of membrane transport proteins. Structurally, two... (Review)
Review
The lactose permease (LacY) of is the prototype of the major facilitator superfamily, one of the largest families of membrane transport proteins. Structurally, two pseudo-symmetrical six-helix bundles surround a large internal aqueous cavity. Single binding sites for galactoside and H are positioned at the approximate center of LacY halfway through the membrane at the apex of the internal cavity. These features enable LacY to function by an alternating-access mechanism that can catalyze galactoside/H symport in either direction across the cytoplasmic membrane. The H-binding site is fully protonated under physiological conditions, and subsequent sugar binding causes transition of the ternary complex to an occluded intermediate that can open to either side of the membrane. We review the structural and functional evidence that has provided new insight into the mechanism by which LacY achieves active transport against a concentration gradient.
Topics: Binding Sites; Catabolite Repression; Escherichia coli; Escherichia coli Proteins; Lactose; Monosaccharide Transport Proteins; Protons; Symporters
PubMed: 31147449
DOI: 10.1085/jgp.201912377 -
Current Drug Targets 2020Urea Transporters are a family of membrane channel proteins that facilitate the passive transport of urea across the plasma membrane. UTs are divided into two subgroups,... (Review)
Review
BACKGROUND
Urea Transporters are a family of membrane channel proteins that facilitate the passive transport of urea across the plasma membrane. UTs are divided into two subgroups, UT-A and UT-B. UT-As are primarily located in renal tubule epithelia and UT-Bs are highly expressed in renal descending vasa recta and extrarenal multiple tissues. Various urea transporter knockout mice exhibit low urine concentrating ability, which suggests that UTs are novel diuretic targets. With highthroughput screening of small molecule drug-like compound libraries, various potent UT inhibitors with IC50 at nanomolar level were identified. Furthermore, selective UT inhibitors exhibit diuretic activity without disturbing electrolyte and metabolism balance, which confirms the potential of UTs as diuretic targets and UT inhibitors as novel diuretics that do not cause electrolyte imbalance.
OBJECTIVE
This review article summarizes the identification and validation of urea transporter as a potential diuretic target and the discovery of small molecule UT inhibitors as a novel type of diuretics.
CONCLUSION
UTs are a potential diuretic target. UT inhibitors play significant diuresis and can be developed to diuretics without disturbing electrolyte balance.
Topics: Animals; Cell Line; Diuresis; Diuretics; Humans; Membrane Transport Proteins; Mice; Mice, Knockout; Small Molecule Libraries; Structure-Activity Relationship; Urea; Water-Electrolyte Balance; Urea Transporters
PubMed: 31782365
DOI: 10.2174/1389450120666191129101915 -
Basic & Clinical Pharmacology &... Feb 2024
Topics: Membrane Transport Proteins; Membrane Proteins; Carrier Proteins; Biological Transport
PubMed: 37945540
DOI: 10.1111/bcpt.13960 -
Chemical Reviews May 2021The biology of mycobacteria is dominated by a complex cell envelope of unique composition and structure and of exceptionally low permeability. This cell envelope is the... (Review)
Review
The biology of mycobacteria is dominated by a complex cell envelope of unique composition and structure and of exceptionally low permeability. This cell envelope is the basis of many of the pathogenic features of mycobacteria and the site of susceptibility and resistance to many antibiotics and host defense mechanisms. This review is focused on the transporters that assemble and functionalize this complex structure. It highlights both the progress and the limits of our understanding of how (lipo)polysaccharides, (glyco)lipids, and other bacterial secretion products are translocated across the different layers of the cell envelope to their final extra-cytoplasmic location. It further describes some of the unique strategies evolved by mycobacteria to import nutrients and other products through this highly impermeable barrier.
Topics: Cell Membrane; Cell Wall; Membrane Lipids; Membrane Transport Proteins; Mycobacterium; Organelle Biogenesis
PubMed: 33170669
DOI: 10.1021/acs.chemrev.0c00869 -
Proceedings of the National Academy of... Oct 2023Bacteria produce a structural layer of peptidoglycan (PG) that enforces cell shape, resists turgor pressure, and protects the cell. As bacteria grow and divide, the...
Bacteria produce a structural layer of peptidoglycan (PG) that enforces cell shape, resists turgor pressure, and protects the cell. As bacteria grow and divide, the existing layer of PG is remodeled and PG fragments are released. Enterics such as go to great lengths to internalize and reutilize PG fragments. is estimated to break down one-third of its cell wall, yet only loses ~0 to 5% of meso-diaminopimelic acid, a PG-specific amino acid, per generation. Two transporters were identified early on to possibly be the primary permease that facilitates PG fragment recycling, i) AmpG and ii) the Opp ATP binding cassette transporter in conjunction with a PG-specific periplasmic binding protein, MppA. The contribution of each transporter to PG recycling has been debated. Here, we have found that AmpG and MppA/Opp are differentially regulated by carbon source and growth phase. In addition, MppA/Opp is uniquely capable of high-affinity scavenging of muropeptides from growth media, demonstrating that AmpG and MppA/Opp allow for different strategies of recycling PG fragments. Altogether, this work clarifies environmental contexts under which utilizes distinct permeases for PG recycling and explores how scavenging by MppA/Opp could be beneficial in mixed communities.
Topics: Membrane Transport Proteins; Escherichia coli; Peptidoglycan; Bacterial Proteins; Bacteria; Cell Wall
PubMed: 37871219
DOI: 10.1073/pnas.2308940120 -
Microbiology (Reading, England) Nov 2022ATP-binding cassette (ABC) transporters are one of the largest protein superfamilies and are found in all living organisms. These transporters use the energy from ATP... (Review)
Review
ATP-binding cassette (ABC) transporters are one of the largest protein superfamilies and are found in all living organisms. These transporters use the energy from ATP binding and hydrolysis to transport various substrates. In this review, we focus on the structural and functional aspects of ABC transporters, with special emphasis on type VII ABC transporters, a newly defined class possessing characteristic structures. A notable feature of type VII ABC transporters is that they assemble into tripartite complexes that span both the inner and outer membranes of Gram-negative bacteria. One of the original type VII ABC transporters, which possesses all characteristic features of this class, is the macrolide efflux transporter MacB. Recent structural analyses of MacB and homologue proteins revealed the unique mechanisms of substrate translocation by type VII ABC transporters.
Topics: ATP-Binding Cassette Transporters; Models, Molecular; Membrane Transport Proteins; Biological Transport; Adenosine Triphosphate
PubMed: 36409601
DOI: 10.1099/mic.0.001257 -
Trends in Biochemical Sciences Sep 2021Elevator-type transporters are a group of proteins translocating nutrients and metabolites across cell membranes. Despite structural and functional differences,... (Review)
Review
Elevator-type transporters are a group of proteins translocating nutrients and metabolites across cell membranes. Despite structural and functional differences, elevator-type transporters use a common mechanism of substrate translocation via reversible movements of a mobile core domain (the elevator), which includes the substrate binding site, along a rigid scaffold domain, stably anchored in the plasma membrane. How substrate specificity is determined in elevator transporters remains elusive. Here, I discuss how a recent report on the sliding elevator mechanism, seen under the context of genetic analysis of a prototype fungal transporter, sheds light on how specificity might be genetically modified. I propose that flexible specificity alterations might occur by 'loosening' of the sliding mechanism from tight coupling to substrate binding.
Topics: Aspergillus nidulans; Biological Transport; Fungal Proteins; Membrane Transport Proteins; Substrate Specificity
PubMed: 33903007
DOI: 10.1016/j.tibs.2021.03.007 -
Biochimica Et Biophysica Acta.... Jun 2024The discovery of MICU1 as gatekeeper of mitochondrial calcium (Ca) entry has transformed our understanding of Ca flux. Recent studies revealed an additional role of... (Review)
Review
The discovery of MICU1 as gatekeeper of mitochondrial calcium (Ca) entry has transformed our understanding of Ca flux. Recent studies revealed an additional role of MICU1 as a Ca sensor at MICOS (mitochondrial contact site and cristae organizing system). MICU1's presence at MICOS suggests its involvement in coordinating Ca signaling and mitochondrial ultrastructure. Besides its role in Ca regulation, MICU1 influences cellular signaling pathways including transcription, epigenetic regulation, metabolism, and cell death, thereby affecting human health. Here, we summarize recent findings on MICU1's canonical and noncanonical functions, and its relevance to human health and diseases.
Topics: Humans; Mitochondria; Calcium; Mitochondrial Membrane Transport Proteins; Calcium Signaling; Calcium-Binding Proteins; Animals; Cation Transport Proteins
PubMed: 38555977
DOI: 10.1016/j.bbamcr.2024.119714 -
International Journal of Molecular... Aug 2022Facilitative sugar transporters (GLUTs) are the primary method of sugar uptake in all mammalian cells. There are 14 different types of those transmembrane proteins, but... (Review)
Review
Facilitative sugar transporters (GLUTs) are the primary method of sugar uptake in all mammalian cells. There are 14 different types of those transmembrane proteins, but they transport only a handful of substrates, mainly glucose and fructose. This overlap and redundancy contradict the natural tendency of cells to conserve energy and resources, and has led researchers to hypothesize that different GLUTs partake in more metabolic roles than just sugar transport into cells. Understanding those roles will lead to better therapeutics for a wide variety of diseases and disorders. In this review we highlight recent discoveries of the role GLUTs play in different diseases and disease treatments.
Topics: Animals; Biological Transport; Fructose; Glucose; Glucose Transport Proteins, Facilitative; Mammals; Membrane Transport Proteins
PubMed: 35955833
DOI: 10.3390/ijms23158698