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Palmitoylation

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https://www.readbyqxmd.com/read/28636818/critical-temperature-of-1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine-monolayers-and-its-possible-biological-relevance
#1
Jordi Hernandez Borrell, Oscar Domenech
Since transmembrane proteins (TMPs) can be obtained with sufficient purity for x-ray diffraction studies more frequently than decades ago, their mechanisms of action may now be elucidated. One of the pending issues is the actual interplay between transmembrane proteins and membrane lipids. There is strong evidence of the involvement of specific lipids with some membrane proteins, such as the potassium crystallographically sited activation channel (KcsA) of Streptomyces lividans and the secondary transporter of lactose LacY of Escherichia coli, the activities of which are associated with the presence of anionic phospholipids such as the phosphatidylglycerol (PG) and phosphatidyethanolamine (PE), respectively...
June 21, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28634855/alpha-linolenic-acid-decreases-apoptosis-and-oxidized-phospholipids-in-cardiomyocytes-during-ischemia-reperfusion
#2
Riya Ganguly, Devin Hasanally, Aleksandra Stamenkovic, Thane G Maddaford, Rakesh Chaudhary, Grant N Pierce, Amir Ravandi
The omega-3 fatty acid, alpha linolenic acid (ALA) found in plant-derived foods induces significant cardiovascular benefits when ingested. ALA may be cardioprotective during ischemia; however, the mechanism(s) responsible for this effect is unknown. Isolated adult rat cardiomyocytes were exposed to medium containing ALA for 24 h and then exposed to non-ischemic (control), simulated ischemia (ISCH), or simulated ischemia/reperfusion (IR) conditions. Cardiomyocyte phospholipids were extracted and analyzed by an HPLC/electrospray ionization tandem mass spectrometry system...
June 20, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28630138/targeting-the-ras-palmitoylation-depalmitoylation-cycle-in-cancer
#3
REVIEW
David Tse Shen Lin, Nicholas G Davis, Elizabeth Conibear
The Ras proteins are well-known drivers of many cancers and thus represent attractive targets for the development of anticancer therapeutics. Inhibitors that disrupt the association of the Ras proteins with membranes by blocking the addition of the farnesyl lipid moiety to the Ras C-terminus failed in clinical trials. Here, we explore the possibility of targeting a second lipid modification, S-acylation, commonly referred to as palmitoylation, as a strategy to disrupt the membrane interaction of specific Ras isoforms...
June 19, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28621883/determination-of-the-serine-palmitoyl-transferase-inhibitor-myriocin-by-electrospray-and-q-trap-mass-spectrometry
#4
Giuseppe Matteo Campisi, Paola Signorelli, Jessica Rizzo, Claudio Ghilardi, Jacopo Antognetti, Anna Caretti, Jelena S Lazarevic, Enrica Strettoi, Elena Novelli, Riccardo Ghidoni, Federico Maria Rubino, Rita Paroni
Myriocin, is a potent inhibitor of serine-palmitoyl-transferase, the first and rate-determining enzyme in the sphingolipids biosynthetic pathway. This study developed, validated and applied a LC-MS/MS method to measure Myriocin in minute specimens of animal tissue. The chemical analog 14-OH-Myriocin is used as the internal standard. The two molecules are extracted from the tissue homogenate by solid-phase extraction, separated by gradient reverse-phase liquid chromatography and measured by negative ion electrospray mass spectrometry in the triple quadrupole...
June 16, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28617626/understanding-the-rules-governing-ncx1-palmitoylation
#5
Fiona Plain, Dionne Turnbull, Niall J Fraser, William Fuller
No abstract text is available yet for this article.
June 15, 2017: Channels
https://www.readbyqxmd.com/read/28608875/model-membrane-size-dependent-amyloidogenesis-of-alzheimer-s-amyloid-%C3%AE-peptides
#6
Misaki Kinoshita, Erina Kakimoto, Mayu S Terakawa, Yuxi Lin, Tatsuya Ikenoue, Masatomo So, Toshihiko Sugiki, Ayyalusamy Ramamoorthy, Yuji Goto, Young-Ho Lee
We herein report the mechanism of amyloid formation of amyloid-β (Aβ) peptides on small (SUV) and large unilamellar vesicles (LUVs), which consist of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipids. Although Aβ1-42 formed fibrils on SUVs at all POPC concentrations used, the lag time, elongation rate, maximum thioflavin T intensity, and fibrillar morphology were distinct, indicating polymorphic amyloid formation. LUVs, at low POPC concentrations, did not markedly affect fibrillation kinetics; however, increases in POPC concentrations suppressed amyloid formation...
June 21, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28607426/analysis-of-the-brain-palmitoyl-proteome-using-both-acyl-biotin-exchange-and-acyl-resin-assisted-capture-methods
#7
Matthew J Edmonds, Bethany Geary, Mary K Doherty, Alan Morgan
Palmitoylation is a reversible post-translational protein modification in which palmitic acid is added to cysteine residues, allowing association with different cellular membranes and subdomains. Recently, techniques have been developed to identify palmitoylation on a proteome-wide scale in order to reveal the full cellular complement of palmitoylated proteins. However, in the studies reported to date, there is considerable variation between the sets of identified palmitoyl-proteins and so there remains some uncertainty over what constitutes the definitive complement of palmitoylated proteins even in well-studied tissues such as brain...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28606576/insulin-sensitizers-improve-the-glp-1-secretion-and-the-amount-of-intestinal-l-cells-on-high-fat-diet-induced-catch-up-growth
#8
Juan Zheng, Kang-Li Xiao, Lulu Chen, Chaodong Wu, Xiang Hu, Tianshu Zeng, Xiao-Qian Chen, Wen-Juan Li, Xiuling Deng, Huiqing Li, Yu-Ming Li
OBJECTIVE: The aim of this study was to investigate whether insulin resistance can result in impaired glucagon-like peptide (GLP)-1 secretion and to determine whether insulin-sensitizing drugs could improve the secretion of GLP-1 in catch-up growth rats. METHODS: Male Sprague Dawley rats were used to establish a catch-up growth model. At the end of weeks 6 and 14, these rats were euthanized to measure energy intake, body weight, plasma triacylglycerol, and nonesterified fatty acid...
July 2017: Nutrition
https://www.readbyqxmd.com/read/28602500/dynamic-protein-acylation-new-substrates-mechanisms-and-drug-targets
#9
REVIEW
Thomas Lanyon-Hogg, Monica Faronato, Remigiusz A Serwa, Edward W Tate
Post-translational attachment of lipids to proteins is found in all organisms, and is important for many biological processes. Acylation with myristic and palmitic acids are among the most common lipid modifications, and understanding reversible protein palmitoylation dynamics has become a particularly important goal. Linking acyltransferase enzymes to disease states can be challenging due to a paucity of robust models, compounded by functional redundancy between many palmitoyl transferases; however, in cases such as Wnt or Hedgehog signalling, small molecule inhibitors have been identified, with some progressing to clinical trials...
June 8, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28600323/rab7-palmitoylation-is-required-for-efficient-endosome-to-tgn-trafficking
#10
Graziana Modica, Olga Skorobogata, Etienne Sauvageau, Adriano Vissa, Christopher M Yip, Peter K Kim, Hugo Wurtele, Stephane Lefrancois
Retromer is a multimeric protein complex that mediates endosome-to-TGN and endosome-to-plasma membrane trafficking of integral membrane proteins. Dysfunction of this complex has been linked to Alzheimer's and Parkinson's disease. The recruitment of retromer to endosomes is regulated by Rab7 to coordinate endosome-to- TGN trafficking of cargo-receptor complexes. Rab7 is also required for the degradation of internalized integral membrane proteins such as the epidermal growth factor receptor. We found that Rab7 is palmitoylated and that this modification is not required for membrane anchoring...
June 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28598967/mitochondrial-respiration-and-ros-emission-during-%C3%AE-oxidation-in-the-heart-an-experimental-computational-study
#11
Sonia Cortassa, Steven J Sollott, Miguel A Aon
Lipids are main fuels for cellular energy and mitochondria their major oxidation site. Yet unknown is to what extent the fuel role of lipids is influenced by their uncoupling effects, and how this affects mitochondrial energetics, redox balance and the emission of reactive oxygen species (ROS). Employing a combined experimental-computational approach, we comparatively analyze β-oxidation of palmitoyl CoA (PCoA) in isolated heart mitochondria from Sham and streptozotocin (STZ)-induced type 1 diabetic (T1DM) guinea pigs (GPs)...
June 9, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28597297/intrinsic-protein-disorder-in-oncogenic-kras-signaling
#12
REVIEW
Ruth Nussinov, Hyunbum Jang, Chung-Jung Tsai, Tsung-Jen Liao, Shuai Li, David Fushman, Jian Zhang
How Ras, and in particular its most abundant oncogenic isoform K-Ras4B, is activated and signals in proliferating cells, poses some of the most challenging questions in cancer cell biology. In this paper, we ask how intrinsically disordered regions in K-Ras4B and its effectors help promote proliferative signaling. Conformational disorder allows spanning long distances, supports hinge motions, promotes anchoring in membranes, permits segments to fulfil multiple roles, and broadly is crucial for activation mechanisms and intensified oncogenic signaling...
June 8, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28597209/molecular-dynamics-simulation-reveals-unique-interplays-between-a-tarantula-toxin-and-lipid-membranes
#13
Lei Wu, Si-Si Xie, Er Meng, Wen-Ying Li, Long Liu, Dong-Yi Zhang
Tarantula toxins compose an important class of spider toxins that target ion channels, and some are known to interact with lipid membranes. In this study, we focus on a tarantula toxin, Jingzhaotoxin-III (JZTx-III) that specifically targets the cardiac voltage-gated sodium channel Na[Formula: see text]1.5 and is suspected to be able to interact with lipid membranes. Here, we use an all-atom model and long-term molecular dynamics simulations to investigate the interactions between JZTx-III and lipid membranes of different compositions...
June 8, 2017: Journal of Membrane Biology
https://www.readbyqxmd.com/read/28596839/structure-specific-effects-of-lipidated-oxytocin-analogs-on-intracellular-calcium-levels-parental-behavior-and-oxytocin-concentrations-in-the-plasma-and-cerebrospinal-fluid-in-mice
#14
Stanislav M Cherepanov, Shigeru Yokoyama, Akira Mizuno, Wataru Ichinose, Olga Lopatina, Anna A Shabalova, Alla B Salmina, Yasuhiko Yamamoto, Hiroshi Okamoto, Satoshi Shuto, Haruhiro Higashida
Oxytocin (OT) is a neuroendocrine nonapeptide that plays an important role in social memory and behavior. Nasal administration of OT has been shown to improve trust in healthy humans and social interaction in autistic subjects in some clinical trials. As a central nervous system (CNS) drug, however, OT has two unfavorable characteristics: OT is short-acting and shows poor permeability across the blood-brain barrier, because it exists in charged form in the plasma and has short half-life. To overcome these drawbacks, an analog with long-lasting effects is required...
February 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28594046/balancing-the-intermolecular-forces-in-peptide-amphiphiles-for-controlling-self-assembly-transitions
#15
C J Buettner, A J Wallace, S Ok, A A Manos, M J Nicholl, A Ghosh, M F Tweedle, J E Goldberger
While the influence of alkyl chain length and headgroup size on self-assembly behaviour has been well-established for simple surfactants, the rational control over the pH- and concentration-dependent self-assembly behaviour in stimuli responsive peptides remains an elusive goal. Here, we show that different amphiphilic peptides can have similar self-assembly phase diagrams, providing the relative strengths of the attractive and repulsive forces are balanced. Using palmitoyl-YYAAEEEEK(DO3A:Gd)-NH2 and palmitoyl-YAAEEEEK(DO3A:Gd)-NH2 as controls, we show that reducing hydrophobic attractive forces through fewer methylene groups in the alkyl chain will lead to a similar self-assembly phase diagram as increasing the electrostatic repulsive forces via the addition of a glutamic acid residue...
June 21, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28591608/ceramide-c16-is-a-versatile-modulator-of-phosphatidylethanolamine-polymorphism
#16
Mahmoudreza Doroudgar, Michel Lafleur
Ceramide-C16 (CerC16) is a sphingolipid associated with several diseases like diabetes, obesity, Parkinson disease, and certain types of cancers. As a consequence, research efforts are devoted to identify the impact of CerC16 on the behavior of membranes, and to understand how it is involved in these diseases. In this work, we investigated the impacts of CerC16 (up to 20 mol %) on the lipid polymorphism of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), using differential scanning calorimetry, and sequential (2)H and (31)P solid-state nuclear magnetic resonance spectroscopy...
June 6, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28591606/influence-of-cholesterol-on-the-oxygen-permeability-of-membranes-insight-from-atomistic-simulations
#17
Rachel J Dotson, Casey R Smith, Kristina Bueche, Gary Angles, Sally C Pias
Cholesterol is widely known to alter the physical properties and permeability of membranes. Several prior works have implicated cell membrane cholesterol as a barrier to tissue oxygenation, yet a good deal remains to be explained with regard to the mechanism and magnitude of the effect. We use molecular dynamics simulations to provide atomic-resolution insight into the influence of cholesterol on oxygen diffusion across and within the membrane. Our simulations show strong overall agreement with published experimental data, reproducing the shapes of experimental oximetry curves with high accuracy...
June 6, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28589930/dynamic-alterations-in-decoy-vegf-receptor-1-stability-regulate-angiogenesis
#18
Joshua M Boucher, Ryan P Clark, Diana C Chong, Kathryn M Citrin, Lyndsay A Wylie, Victoria L Bautch
Blood vessel expansion is driven by sprouting angiogenesis of endothelial cells, and is essential for development, wound healing and disease. Membrane-localized vascular endothelial growth factor receptor-1 (mVEGFR1) is an endothelial cell-intrinsic decoy receptor that negatively modulates blood vessel morphogenesis. Here we show that dynamic regulation of mVEGFR1 stability and turnover in blood vessels impacts angiogenesis. mVEGFR1 is highly stable and constitutively internalizes from the plasma membrane. Post-translational palmitoylation of mVEGFR1 is a binary stabilization switch, and ligand engagement leads to depalmitoylation and lysosomal degradation...
June 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28587835/effect-of-physicochemical-properties-of-peptides-from-soy-protein-on-their-antimicrobial-activity
#19
Ning Xiang, Yuan Lyu, Xiao Zhu, Arun K Bhunia, Ganesan Narsimhan
Antimicrobial peptides (AMPs) kill microbial cells through insertion and damage/permeabilization of the cytoplasmic cell membranes and has applications in food safety and antibiotic replacement. Soy protein is an attractive, abundant natural source for commercial production of AMPs. In this research, explicit solvent molecular dynamics (MD) simulation was employed to investigate the effects of (i) number of total and net charges, (ii) hydrophobicity (iii) hydrophobic moment and (iv) helicity of peptides from soy protein on their ability to bind to lipid bilayer and their transmembrane aggregates to form pores...
June 3, 2017: Peptides
https://www.readbyqxmd.com/read/28585804/membrane-interactions-of-hiapp-monomer-and-oligomer-with-lipid-membranes-by-molecular-dynamics-simulations
#20
Mingzhen Zhang, Baiping Ren, Yonglan Liu, Guizhao Liang, Yan Sun, Lijian Xu, Jie Zheng
Interaction of human islet amyloid polypeptide (hIAPP) peptides with cell membrane is crucial for the understanding of amyloid toxicity associated with Type II diabetes (T2D). While it is known that the hIAPP-membrane interactions are considered to promote hIAPP aggregation into fibrils and induce membrane disruption, the membrane-induced conformation, orientation, aggregation, and adsorption behaviors of hIAPP peptides have not been well understood at atomic level. Herein, we perform all-atom explicit-water molecular dynamics (MD) simulations to study the adsorption, orientation, and surface interaction of hIAPP aggregates with different sizes (monomer to tetramer) and conformations (monomer with α-helix and tetramer with β-sheet-rich U-turn) upon adsorption on the lipid bilayers composed of both pure zwitterionic POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and mixed anionic POPC/POPE (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine) (3:1) lipids...
June 6, 2017: ACS Chemical Neuroscience
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