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1.
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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2.
New formaldehyde-free adhesives for wood manufacturing: In vitro evaluation of potential toxicity of fine dust collected during wood sawing using a new experimental model to simulate occupational inhalation exposure.
Cavallo, D, Fresegna, AM, Ciervo, A, Ursini, CL, Maiello, R, Del Frate, V, Ferrante, R, Mabilia, R, Pizzo, B, Grossi, B, et al
Toxicology. 2022;:153085
Abstract
Formaldehyde mainly emitted from wood adhesives, finishing materials, paint for furniture represents, together with wood dust, a potential carcinogenic risk for wood workers. Aims of this multidisciplinary study are to investigate the possibility of replacing urea-formaldehyde (UF) adhesives in the wood industry with organic and/or inorganic-based glues to obtain a final less toxic product and to evaluate the potential toxicity of wood glued with such new adhesives. For this purpose we selected poplar wood to test an organic new adhesive HBP (Hemp Based Protein), a mixture of hemp flour and cross-linker PAE (polyaminoamide epichlorohydrin), and spruce wood to test an inorganic adhesive geopolymer K-PSS (potassium-polysiloxosialate) plus polyvinyl acetate. For the poplar wood, we also used a commercial panel glued with UF for comparison. We reproduced occupational inhalation exposure during sawing activities of mentioned woods, collected and characterized the wood dusts emitted during sawing and evaluated in vitro their potential cyto-genotoxic and inflammatory effects. We used human lung cells (A549) exposed for 24 h to 20 and 100 μg/mL of collected PM2.5 wood dust. We found that both the new adhesives wood dusts induced a slightly higher apoptotic effect than untreated natural wood dusts particularly in spruce wood. Only geopolymer K-PSS wood dust induced membrane damage at the highest concentration and direct and oxidative DNA damage that could be explained by the different chemical composition and the lower particle sizes in respect to organic HBP adhesive wood dust. We found slight induction of IL-6 release, not influenced by K-PSS treatment, at the highest concentration in spruce wood. For poplar wood, IL-6 and IL-8 induction was found particularly for untreated and UF-treated wood at the highest concentration, where hemp adhesive treatment induced lower inflammation while at lower concentration similar slight cytokine induction was found for all tested wood dusts. This preliminary study shows that natural adhesives used to replace UF adhesives represent an interesting alternative, particularly the organic hemp-based adhesive showing very low toxicity.
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A single dual-targeting fluorescent probe enables exploration of the correlation between the plasma membrane and lysosomes.
Yu, S, Wu, S, Zhang, J, Zhao, X, Liu, X, Yi, X, Li, X
Journal of materials chemistry. B. 2022;(4):582-588
Abstract
The interactions between organelles can maintain normal cell activity. Lysosomes, as waste disposal systems of cells, have many important interactions with the plasma membrane, especially in the repair of cracked plasma membrane. Unfortunately, a way to study the relationship between them synchronously is still lacking. Therefore, in this work, we constructed a dual-targeting probe (Mem-Lyso) to simultaneously visualize the plasma membrane and lysosomes for the first time. Taking advantage of dual-targeting, the probe Mem-Lyso could successfully track and analyze the dynamic changes of the plasma membrane and lysosomes in different bioprocesses. The experimental results demonstrated that, compared to the normal status, there was obvious fusion between the plasma membrane and lysosomes in the apoptosis process. Furthermore, because of the sensitivity to polarity, Mem-Lyso could label the plasma membrane and lysosomes with red and yellow colors in cells, respectively. Moreover, the skeleton and gastrointestinal wall of zebrafish were visualized by dual-color imaging, respectively. More importantly, the dual-targeting property endowed Mem-Lyso with the ability to spatially distinguish the cholesterol (CL) content in the plasma membrane, which provided a potential detection tool for biological research and diagnosis of related diseases.
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4.
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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5.
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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6.
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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7.
Cell-Penetrating Peptides: Correlation between Peptide-Lipid Interaction and Penetration Efficiency.
Her Choong, F, Keat Yap, B
Chemphyschem : a European journal of chemical physics and physical chemistry. 2021;(5):493-498
Abstract
Cell-penetrating peptides are used in the delivery of peptides and biologics, with some cell-penetrating peptides found to be more efficient than others. The exact mechanism of how they interact with the cell membrane and penetrate it, however, remains unclear. This study attempts to investigate the difference in free energy profiles of three cell-penetrating peptides (TAT, CPP1 and CPP9) with a model lipid bilayer (DOPC) using molecular dynamics pulling simulations with umbrella sampling. Potential mean force (PMF) and free energy barrier between the peptides and DOPC are determined using WHAM analysis and MM-PBSA analysis, respectively. CPP9 is found to have the smallest PMF value, followed by CPP1 and TAT, consistent with the experimental data. YDEGE peptide, however, does not give the highest PMF value, although it is a non-cell-permeable peptide. YDEGE is also found to form water pores, alongside with TAT and CPP9, suggesting that it is difficult to distinguish true water pore formation from artefacts arising from pulling simulations. On the contrary, free energy analysis of the peptide-DOPC complex at the lipid-water interface with MM-PBSA provides results consistent with experimental data with CPP9 having the least interaction with DOPC and lowest free energy barrier, followed by CPP1, TAT and YDEGE. These findings suggest that peptide-lipid interaction at the lipid-water interface has a direct correlation with the penetration efficiency of peptides across the lipid bilayer.
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8.
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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9.
Phosphorylation of meprin β controls its cell surface abundance and subsequently diminishes ectodomain shedding.
Armbrust, F, Bickenbach, K, Koudelka, T, Tholey, A, Pietrzik, C, Becker-Pauly, C
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2021;(7):e21677
Abstract
Meprin β is a zinc-dependent metalloprotease exhibiting a unique cleavage specificity with strong preference for acidic amino acids at the cleavage site. Proteomic studies revealed a diverse substrate pool of meprin β including the interleukin-6 receptor (IL-6R) and the amyloid precursor protein (APP). Dysregulation of meprin β is often associated with pathological conditions such as chronic inflammation, fibrosis, or Alzheimer's disease (AD). The extracellular regulation of meprin β including interactors, sheddases, and activators has been intensively investigated while intracellular regulation has been barely addressed in the literature. This study aimed to analyze C-terminal phosphorylation of meprin β with regard to cell surface expression and proteolytic activity. By immunoprecipitation of endogenous meprin β from the colon cancer cell line Colo320 and subsequent LC-MS analysis, we identified several phosphorylation sites in its C-terminal region. Here, T694 in the C-terminus of meprin β was the most preferred residue after phorbol 12-myristate 13-acetate (PMA) stimulation. We further demonstrated the role of protein kinase C (PKC) isoforms for meprin β phosphorylation and identified the involvement of PKC-α and PKC-β. As a result of phosphorylation, the meprin β activity at the cell surface is reduced and, consequently, the extent of substrate cleavage is diminished. Our data indicate that this decrease of the surface activity is caused by the internalization and degradation of meprin β.
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10.
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.