Effects of Omega-3 Fatty Acids on Immune Cells Gutiérrez, Saray; Svahn, Sara L; Johansson, Maria E
International journal of molecular sciences,
10/2019, Volume:
20, Issue:
20
Journal Article
Peer reviewed
Open access
Alterations on the immune system caused by omega-3 fatty acids have been described for 30 years. This family of polyunsaturated fatty acids exerts major alterations on the activation of cells from ...both the innate and the adaptive immune system, although the mechanisms for such regulation are diverse. First, as a constitutive part of the cellular membrane, omega-3 fatty acids can regulate cellular membrane properties, such as membrane fluidity or complex assembly in lipid rafts. In recent years, however, a new role for omega-3 fatty acids and their derivatives as signaling molecules has emerged. In this review, we describe the latest findings describing the effects of omega-3 fatty acids on different cells from the immune system and their possible molecular mechanisms.
The folding and insertion of integral β-barrel membrane proteins into the outer membrane of Gram-negative bacteria is required for viability and bacterial pathogenesis. Unfortunately, the lack of ...selective and potent modulators to dissect β-barrel folding in vivo has hampered our understanding of this fundamental biological process. Here, we characterize amonoclonal antibody that selectively inhibits an essential component of the Escherichia coli β-barrel assembly machine, BamA. In the absence of complement or other immune factors, the unmodified antibody MAB1 demonstrates bactericidal activity against an E. coli strain with truncated LPS. Direct binding of MAB1 to an extracellular BamA epitope inhibits its β-barrel folding activity, induces periplasmic stress, disrupts outer membrane integrity, and kills bacteria. Notably, resistance to MAB1-mediated killing reveals a link between outermembrane fluidity and protein folding by BamA in vivo, underscoring the utility of this antibody for studying β-barrel membrane protein folding within a living cell. Identification of this BamA antagonist highlights the potential for new mechanisms of antibiotics to inhibit Gram-negative bacterial growth by targeting extracellular epitopes.
The fluid mosaic model of Singer and Nicolson (1972) is a commonly used representation of the cell membrane structure and dynamics. However a number of features, the result of four decades of ...research, must be incorporated to obtain a valid, contemporary version of the model. Among the novel aspects to be considered are: (i) the high density of proteins in the bilayer, that makes the bilayer a molecularly “crowded” space, with important physiological consequences; (ii) the proteins that bind the membranes on a temporary basis, thus establishing a continuum between the purely soluble proteins, never in contact with membranes, and those who cannot exist unless bilayer-bound; (iii) the progress in our knowledge of lipid phases, the putative presence of non-lamellar intermediates in membranes, and the role of membrane curvature and its relation to lipid geometry, (iv) the existence of lateral heterogeneity (domain formation) in cell membranes, including the transient microdomains known as rafts, and (v) the possibility of transient and localized transbilayer (flip-flop) lipid motion. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy.
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•The fluid mosaic model of membrane structure by Singer and Nicolson was published in 1972.•The model remains essentially valid.•However new and important data must be incorporated into the model.
Palladium (Pd)-based membranes have received a great deal of attention from both academia and industry thanks to their ability to selectively separate hydrogen from gas streams. The integration of ...such membranes with appropriate catalysts in membrane reactors allows for hydrogen production with CO2 capture that can be applied in smaller bioenergy or combined heat and power (CHP) plants, as well as in large-scale power plants. Pd-based membranes are therefore regarded as a Key Enabling Technology (KET) to facilitate the transition towards a knowledge-based, low-carbon, and resource-efficient economy. This Special Issue of the journal Membranes on “Pd-based Membranes: Overview and Perspectives” contains nine peer-reviewed articles. Topics include manufacturing techniques, understanding of material phenomena, module and reactor design, novel applications, and demonstration efforts and industrial exploitation.
The recent rapid accumulation of knowledge on the dynamics and structure of the plasma membrane has prompted major modifications of the textbook fluid-mosaic model. However, because the new data have ...been obtained in a variety of research contexts using various biological paradigms, the impact of the critical conceptual modifications on biomedical research and development has been limited. In this review, we try to synthesize our current biological, chemical, and physical knowledge about the plasma membrane to provide new fundamental organizing principles of this structure that underlie every molecular mechanism that realizes its functions. Special attention is paid to signal transduction function and the dynamic aspect of the organizing principles. We propose that the cooperative action of the hierarchical three-tiered mesoscale (2-300 nm) domains--actin-membrane-skeleton induced compartments (40-300 nm), raft domains (2-20 nm), and dynamic protein complex domains (3-10 nm)--is critical for membrane function and distinguishes the plasma membrane from a classical Singer-Nicolson-type model.
Membrane proteins are essential for the diverse biological functions of the cells and intercellular communication in living organisms. With the recent developments in the methodologies, the research ...on membrane proteins has been undergoing a major transformation. In this informative book, the biological and dynamic behaviour of membrane proteins are introduced, discussed, and reviewed by some of the leading researchers in the field. The main objective of this compendium is to present the recent research in the fundamental and advanced concepts and methodologies used for studying membrane proteins. Membrane protein purification and reconstitution, protein–lipid interaction, ion/substrate transport, conformational and functional dynamics, the interaction of infectious agents, cell death, and organelle morphology are among the topics that are covered. This reprint is intended for a broad range of novice and experienced scientists with different levels of experience, from biophysicists and biochemists to microbiologists, cell biologists, and physiologists.
Bacteria deploy weapons to kill their neighbours during competition for resources and to aid survival within microbiomes. Colicins were the first such antibacterial system identified, yet how these ...bacteriocins cross the outer membrane (OM) of Escherichia coli is unknown. Here, by solving the structures of translocation intermediates via cryo‐EM and by imaging toxin import, we uncover the mechanism by which the Tol‐dependent nuclease colicin E9 (ColE9) crosses the bacterial OM. We show that threading of ColE9’s disordered N‐terminal domain through two pores of the trimeric porin OmpF causes the colicin to disengage from its primary receptor, BtuB, and reorganises the translocon either side of the membrane. Subsequent import of ColE9 through the lumen of a single OmpF subunit is driven by the proton‐motive force, which is delivered by the TolQ‐TolR‐TolA‐TolB assembly. Our study answers longstanding questions, such as why OmpF is a better translocator than OmpC, and reconciles the mechanisms by which both Tol‐ and Ton‐dependent bacteriocins cross the bacterial outer membrane.
Synopsis
Colicins were the first antibacterial agents found to be produced by bacteria, yet it has remained unclear how they cross the outer membrane of E. coli. Here, structural and imaging data reveal the mechanism of ColE9 toxin import via the OmpF translocon.
Cryo‐electron microscopy translocon structures of the bacteriocin colicin E9 reveals the early steps of translocation across the outer bacterial membrane.
Translocon formation results in the passive displacement of the colicin from its receptor, BtuB.
Subsequent import of colicin E9 through the lumen of a single OmpF subunit is driven by the proton‐motive force.
Electrostatic properties of the porin lumen explain why colicins are preferentially transported through OmpF rather than OmpC.
Cryo‐EM structures and fluorescence imaging reveal how the Tol‐dependent bacteriocin ColE9 crosses the outer bacterial membrane to exert microbial killing.
Mitochondria are essential organelles with numerous functions in cellular metabolism and homeostasis. Most of the >1,000 different mitochondrial proteins are synthesized as precursors in the cytosol ...and are imported into mitochondria by five transport pathways. The protein import machineries of the mitochondrial membranes and aqueous compartments reveal a remarkable variability of mechanisms for protein recognition, translocation, and sorting. The protein translocases do not operate as separate entities but are connected to each other and to machineries with functions in energetics, membrane organization, and quality control. Here, we discuss the versatility and dynamic organization of the mitochondrial protein import machineries. Elucidating the molecular mechanisms of mitochondrial protein translocation is crucial for understanding the integration of protein translocases into a large network that controls organelle biogenesis, function, and dynamics.
Many proteins must translocate through the protein-conducting Sec61 channel in the eukaryotic endoplasmic reticulum membrane or the SecY channel in the prokaryotic plasma membrane
. Proteins with ...highly hydrophobic signal sequences are first recognized by the signal recognition particle (SRP)
and then moved co-translationally through the Sec61 or SecY channel by the associated translating ribosome. Substrates with less hydrophobic signal sequences bypass the SRP and are moved through the channel post-translationally
. In eukaryotic cells, post-translational translocation is mediated by the association of the Sec61 channel with another membrane protein complex, the Sec62-Sec63 complex
, and substrates are moved through the channel by the luminal BiP ATPase
. How the Sec62-Sec63 complex activates the Sec61 channel for post-translational translocation is not known. Here we report the electron cryo-microscopy structure of the Sec complex from Saccharomyces cerevisiae, consisting of the Sec61 channel and the Sec62, Sec63, Sec71 and Sec72 proteins. Sec63 causes wide opening of the lateral gate of the Sec61 channel, priming it for the passage of low-hydrophobicity signal sequences into the lipid phase, without displacing the channel's plug domain. Lateral channel opening is triggered by Sec63 interacting both with cytosolic loops in the C-terminal half of Sec61 and transmembrane segments in the N-terminal half of the Sec61 channel. The cytosolic Brl domain of Sec63 blocks ribosome binding to the channel and recruits Sec71 and Sec72, positioning them for the capture of polypeptides associated with cytosolic Hsp70
. Our structure shows how the Sec61 channel is activated for post-translational protein translocation.
Cellular membranes are fundamental building blocks regulating an extensive repertoire of biological functions. These structures contain lipids and membrane proteins that are known to laterally ...self-aggregate in the plane of the membrane, forming defined membrane nanoscale domains essential for protein activity. Membrane rafts are described as heterogeneous, dynamic, and short-lived cholesterol- and sphingolipid-enriched membrane nanodomains (10–200 nm) induced by lipid-protein and lipid-lipid interactions. Those membrane nanodomains have been extensively characterized using model membranes and in silico methods. However, despite the development of advanced fluorescence microscopy techniques, undoubted nanoscale visualization by imaging techniques of membrane rafts in the membrane of unperturbed living cells is still uncompleted, increasing the skepticism about their existence. Here, we broadly review recent biochemical and microscopy techniques used to investigate membrane rafts in living cells and we enumerate persistent open questions to answer before unlocking the mystery of membrane rafts in living cells.
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•Lipid rafts existence in living unperturbed cells is still not fully solved.•Different strategies can be used for visualizing lipid nanodomains in living cells.•Super-resolution microscopy techniques are key techniques to visualize lipid rafts.•Novel membranes probes suitable for super-resolution microscopy are required for membrane research
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