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Bacterial Small Membrane Proteins: the Swiss Army Knife of Regulators at the Lipid Bilayer.
Yadavalli, SS, Yuan, J
Journal of bacteriology. 2022;(1):e0034421
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Abstract
Small membrane proteins represent a subset of recently discovered small proteins (≤100 amino acids), which are a ubiquitous class of emerging regulators underlying bacterial adaptation to environmental stressors. Until relatively recently, small open reading frames encoding these proteins were not designated genes in genome annotations. Therefore, our understanding of small protein biology was primarily limited to a few candidates associated with previously characterized larger partner proteins. Following the first systematic analyses of small proteins in Escherichia coli over a decade ago, numerous small proteins across different bacteria have been uncovered. An estimated one-third of these newly discovered proteins in E. coli are localized to the cell membrane, where they may interact with distinct groups of membrane proteins, such as signal receptors, transporters, and enzymes, and affect their activities. Recently, there has been considerable progress in functionally characterizing small membrane protein regulators aided by innovative tools adapted specifically to study small proteins. Our review covers prototypical proteins that modulate a broad range of cellular processes, such as transport, signal transduction, stress response, respiration, cell division, sporulation, and membrane stability. Thus, small membrane proteins represent a versatile group of physiology regulators at the membrane and the whole cell. Additionally, small membrane proteins have the potential for clinical applications, where some of the proteins may act as antibacterial agents themselves while others serve as alternative drug targets for the development of novel antimicrobials.
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Importance of tyrosine phosphorylation for transmembrane signaling in plants.
Mühlenbeck, H, Bender, KW, Zipfel, C
The Biochemical journal. 2021;(14):2759-2774
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Abstract
Reversible protein phosphorylation is a widespread post-translational modification fundamental for signaling across all domains of life. Tyrosine (Tyr) phosphorylation has recently emerged as being important for plant receptor kinase (RK)-mediated signaling, particularly during plant immunity. How Tyr phosphorylation regulates RK function is however largely unknown. Notably, the expansion of protein Tyr phosphatase and SH2 domain-containing protein families, which are the core of regulatory phospho-Tyr (pTyr) networks in choanozoans, did not occur in plants. Here, we summarize the current understanding of plant RK Tyr phosphorylation focusing on the critical role of a pTyr site ('VIa-Tyr') conserved in several plant RKs. Furthermore, we discuss the possibility of metazoan-like pTyr signaling modules in plants based on atypical components with convergent biochemical functions.
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Structure and Mechanism of Respiratory III-IV Supercomplexes in Bioenergetic Membranes.
Brzezinski, P, Moe, A, Ädelroth, P
Chemical reviews. 2021;(15):9644-9673
Abstract
In the final steps of energy conservation in aerobic organisms, free energy from electron transfer through the respiratory chain is transduced into a proton electrochemical gradient across a membrane. In mitochondria and many bacteria, reduction of the dioxygen electron acceptor is catalyzed by cytochrome c oxidase (complex IV), which receives electrons from cytochrome bc1 (complex III), via membrane-bound or water-soluble cytochrome c. These complexes function independently, but in many organisms they associate to form supercomplexes. Here, we review the structural features and the functional significance of the nonobligate III2IV1/2 Saccharomyces cerevisiae mitochondrial supercomplex as well as the obligate III2IV2 supercomplex from actinobacteria. The analysis is centered around the Q-cycle of complex III, proton uptake by CytcO, as well as mechanistic and structural solutions to the electronic link between complexes III and IV.
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Regulated Intramembrane Proteolysis of ACE2: A Potential Mechanism Contributing to COVID-19 Pathogenesis?
Gonzalez, SM, Siddik, AB, Su, RC
Frontiers in immunology. 2021;:612807
Abstract
Since being identified as a key receptor for SARS-CoV-2, Angiotensin converting enzyme 2 (ACE2) has been studied as one of the potential targets for the development of preventative and/or treatment options. Tissue expression of ACE2 and the amino acids interacting with the spike protein of SARS-CoV-2 have been mapped. Furthermore, the recombinant soluble extracellular domain of ACE2 is already in phase 2 trials as a treatment for SARS-CoV-2 infection. Most studies have continued to focus on the ACE2 extracellular domain, which is known to play key roles in the renin angiotensin system and in amino acid uptake. However, few also found ACE2 to have an immune-modulatory function and its intracellular tail may be one of the signaling molecules in regulating cellular activation. The implication of its immune-modulatory role in preventing the cytokine-storm, observed in severe COVID-19 disease outcomes requires further investigation. This review focuses on the regulated proteolytic cleavage of ACE2 upon binding to inducer(s), such as the spike protein of SARS-CoV, the potential of cleaved ACE2 intracellular subdomain in regulating cellular function, and the ACE2's immune-modulatory function. This knowledge is critical for targeting ACE2 levels for developing prophylactic treatment or preventative measures in SARS-CoV infections.
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Hormonal and environmental signaling pathways target membrane water transport.
Maurel, C, Tournaire-Roux, C, Verdoucq, L, Santoni, V
Plant physiology. 2021;(4):2056-2070
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Abstract
Plant water transport and its molecular components including aquaporins are responsive, across diverse time scales, to an extremely wide array of environmental and hormonal signals. These include water deficit and abscisic acid (ABA) but also more recently identified stimuli such as peptide hormones or bacterial elicitors. The present review makes an inventory of corresponding signalling pathways. It identifies some main principles, such as the central signalling role of ROS, with a dual function of aquaporins in water and hydrogen peroxide transport, the importance of aquaporin phosphorylation that is targeted by multiple classes of protein kinases, and the emerging role of lipid signalling. More studies including systems biology approaches are now needed to comprehend how plant water transport can be adjusted in response to combined stresses.
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The roles of lipids in SARS-CoV-2 viral replication and the host immune response.
Theken, KN, Tang, SY, Sengupta, S, FitzGerald, GA
Journal of lipid research. 2021;:100129
Abstract
The significant morbidity and mortality associated with severe acute respiratory syndrome coronavirus 2 infection has underscored the need for novel antiviral strategies. Lipids play essential roles in the viral life cycle. The lipid composition of cell membranes can influence viral entry by mediating fusion or affecting receptor conformation. Upon infection, viruses can reprogram cellular metabolism to remodel lipid membranes and fuel the production of new virions. Furthermore, several classes of lipid mediators, including eicosanoids and sphingolipids, can regulate the host immune response to viral infection. Here, we summarize the existing literature on the mechanisms through which these lipid mediators may regulate viral burden in COVID-19. Furthermore, we define the gaps in knowledge and identify the core areas in which lipids offer therapeutic promise for severe acute respiratory syndrome coronavirus 2.
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EFA6 in Axon Regeneration, as a Microtubule Regulator and as a Guanine Nucleotide Exchange Factor.
Gonzalez, G, Chen, L
Cells. 2021;(6)
Abstract
Axon regeneration after injury is a conserved biological process that involves a large number of molecular pathways, including rapid calcium influx at injury sites, retrograde injury signaling, epigenetic transition, transcriptional reprogramming, polarized transport, and cytoskeleton reorganization. Despite the numerous efforts devoted to understanding the underlying cellular and molecular mechanisms of axon regeneration, the search continues for effective target molecules for improving axon regeneration. Although there have been significant historical efforts towards characterizing pro-regenerative factors involved in axon regeneration, the pursuit of intrinsic inhibitors is relatively recent. EFA6 (exchange factor for ARF6) has been demonstrated to inhibit axon regeneration in different organisms. EFA6 inhibition could be a promising therapeutic strategy to promote axon regeneration and functional recovery after axon injury. This review summarizes the inhibitory role on axon regeneration through regulating microtubule dynamics and through affecting ARF6 (ADP-ribosylation factor 6) GTPase-mediated integrin transport.
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The role of cell surface sialic acids for SARS-CoV-2 infection.
Sun, XL
Glycobiology. 2021;(10):1245-1253
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Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a new virus that has higher contagious capacity than any other previous human coronaviruses (HCoVs) and causes the current coronavirus disease 2019 pandemic. Sialic acids are a group of nine-carbon acidic α-keto sugars, usually located at the end of glycans of cell surface glycoconjugates and serve as attachment sites for previous HCoVs. It is therefore speculated that sialic acids on the host cell surface could serve as co-receptors or attachment factors for SARS-CoV-2 cell entry as well. Recent in silico modeling, molecular modeling predictions and microscopy studies indicate potential sialic acid binding by SARS-CoV-2 upon cell entry. In particular, a flat sialic acid-binding domain was proposed at the N-terminal domain of the spike protein, which may lead to the initial contact and interaction of the virus on the epithelium followed by higher affinity binding to angiotensin-converting enzyme 2 (ACE2) receptor, likely a two-step attachment fashion. However, recent in vitro and ex vivo studies of sialic acids on ACE2 receptor confirmed an opposite role for SARS-CoV-2 binding. In particular, neuraminidase treatment of epithelial cells and ACE2-expressing 293T cells increased SARS-CoV-2 binding. Furthermore, the ACE2 glycosylation inhibition studies indicate that sialic acids on ACE2 receptor prevent ACE2-spike protein interaction. On the other hand, a most recent study indicates that gangliosides could serve as ligands for receptor-binding domain of SARS-CoV-2 spike protein. This mini-review discusses what has been predicted and known so far about the role of sialic acid for SARS-CoV-2 infection and future research perspective.
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Differential Subcellular Distribution of Cytokinins: How Does Membrane Transport Fit into the Big Picture?
Nedvěd, D, Hošek, P, Klíma, P, Hoyerová, K
International journal of molecular sciences. 2021;(7)
Abstract
Cytokinins are a class of phytohormones, signalling molecules specific to plants. They act as regulators of diverse physiological processes in complex signalling pathways. It is necessary for plants to continuously regulate cytokinin distribution among different organs, tissues, cells, and compartments. Such regulatory mechanisms include cytokinin biosynthesis, metabolic conversions and degradation, as well as cytokinin membrane transport. In our review, we aim to provide a thorough picture of the latter. We begin by summarizing cytokinin structures and physicochemical properties. Then, we revise the elementary thermodynamic and kinetic aspects of cytokinin membrane transport. Next, we review which membrane-bound carrier proteins and protein families recognize cytokinins as their substrates. Namely, we discuss the families of "equilibrative nucleoside transporters" and "purine permeases", which translocate diverse purine-related compounds, and proteins AtPUP14, AtABCG14, AtAZG1, and AtAZG2, which are specific to cytokinins. We also address long-distance cytokinin transport. Putting all these pieces together, we finally discuss cytokinin distribution as a net result of these processes, diverse in their physicochemical nature but acting together to promote plant fitness.
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The plant axis as the command centre for (re)distribution of sucrose and amino acids.
van Bel, AJE
Journal of plant physiology. 2021;:153488
Abstract
Along with the increase in size required for optimal colonization of terrestrial niches, channels for bidirectional bulk transport of materials in land plants evolved during a period of about 100 million years. These transport systems are essentially still in operation - though perfected over the following 400 million years - and make use of hydrostatic differentials. Substances are accumulated or released at the loading and unloading ends, respectively, of the transport channels. The intermediate stretch between the channel termini is bifunctional and executes orchestrated release and retrieval of solutes. Analyses of anatomical and physiological data demonstrate that the release/retrieval zone extends deeper into sources and sinks than is commonly thought and covers usually much more than 99% of the translocation stretch. This review sketches the significance of events in the intermediate stretch for distribution of organic materials over the plant body. Net leakage from the channels does not only serve maintenance and growth of tissues along the pathway, but also diurnal, short-term or seasonal storage of reserve materials, and balanced distribution of organic C- and N-compounds over axial and terminal sinks. Release and retrieval are controlled by plasma-membrane transporters at the vessel/parenchyma interface in the contact pits along xylem vessels and by plasma-membrane transporters at the interface between companion cells and phloem parenchyma along sieve tubes. The xylem-to-phloem pathway vice versa is a bifacial, radially oriented system comprising a symplasmic pathway, of which entrance and exit are controlled at specific membrane checkpoints, and a parallel apoplasmic pathway. A broad range of specific sucrose and amino-acid transporters are deployed at the checkpoint plasma membranes. SUCs, SUTs, STPs, SWEETs, and AAPs, LTHs, CATs are localized to the plasma membranes in question, both in monocots and eudicots. Presence of Umamits in monocots is uncertain. There is some evidence for endo- and exocytosis at the vessel/parenchyma interface supplementary to the transporter-mediated uptake and release. Actions of transporters at the checkpoints are equally decisive for storage and distribution of amino acids and sucrose in monocots and eudicots, but storage and distribution patterns may differ between both taxa. While the majority of reserves is sequestered in vascular parenchyma cells in dicots, lack of space in monocot vasculature urges "outsourcing" of storage in ground parenchyma around the translocation path. In perennial dicots, specialized radial pathways (rays) include the sites for seasonal alternation of storage and mobilization. In dicots, apoplasmic phloem loading and a correlated low rate of release along the path would favour supply with photoassimilates of terminal sinks, while symplasmic phloem loading and a correlated higher rate of release along the path favours supply of axial sinks and transfer to the xylem. The balance between the resource acquisition by terminal and axial sinks is an important determinant of relative growth rate and, hence, for the fitness of plants in various habitats. Body enlargement as the evolutionary drive for emergence of vascular systems and mass transport propelled by hydrostatic differentials.