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Palmitoylation

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https://www.readbyqxmd.com/read/27913102/membrane-permeabilization-induced-by-triton-x-100-the-role-of-membrane-phase-state-and-edge-tension
#1
Bruno Mattei, Rafael B Lira, Katia R Perez, Karin A Riske
Detergents are widely used to solubilize and separate biomembrane components. It is therefore relevant to study and understand the mechanistic details underlying detergent-lipid interactions using biomimetic systems. Here, we have investigated in detail the process of membrane permeabilization and the nature of pores induced by sub-solubilizing concentrations of the detergent Triton X-100 (TX-100) in bilayers composed of palmitoyl oleoyl phosphatidylcholine (POPC), sphingomyelin (SM) and binary mixtures of these phospholipids with 30 mol% cholesterol (chol)...
November 29, 2016: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/27911442/palmitoylation-of-caspase-6-by-hip14-regulates-its-activation
#2
Niels H Skotte, Shaun S Sanders, Roshni R Singaraja, Dagmar E Ehrnhoefer, Kuljeet Vaid, Xiaofan Qiu, Srinivasaragavan Kannan, Chandra Verma, Michael R Hayden
Caspase-6 (CASP6) has an important role in axonal degeneration during neuronal apoptosis and in the neurodegenerative diseases Alzheimer and Huntington disease. Decreasing CASP6 activity may help to restore neuronal function in these and other diseases such as stroke and ischemia, where increased CASP6 activity has been implicated. The key to finding approaches to decrease CASP6 activity is a deeper understanding of the mechanisms regulating CASP6 activation. We show that CASP6 is posttranslationally palmitoylated by the palmitoyl acyltransferase HIP14 and that the palmitoylation of CASP6 inhibits its activation...
December 2, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27905603/pathological-levels-of-glucosylceramide-change-the-biophysical-properties-of-artificial-and-cell-membranes
#3
Ana R P Varela, Ana E Ventura, Ana C Carreira, Aleksander Fedorov, Anthony H Futerman, Manuel Prieto, Liana C Silva
Glucosylceramide (GlcCer) plays an active role in the regulation of various cellular events. Moreover, GlcCer is also a key modulator of membrane biophysical properties, which might be linked to the mechanism of its biological action. In order to understand the biophysical implications of GlcCer on membranes of living cells, we first studied the effect of GlcCer on artificial membranes containing 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), sphingomyelin (SM) and cholesterol (Chol). Using an array of biophysical methods, we demonstrate that at lower GlcCer/Chol ratios, GlcCer stabilizes SM/Chol-enriched liquid-ordered domains...
December 1, 2016: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/27901162/molecular-dynamics-simulations-and-kelvin-probe-force-microscopy-to-study-of-cholesterol-induced-electrostatic-nanodomains-in-complex-lipid-mixtures
#4
E Drolle, W F D Bennett, K Hammond, E Lyman, M Karttunen, Z Leonenko
The molecular arrangement of lipids and proteins within biomembranes and monolayers gives rise to complex film morphologies as well as regions of distinct electrical surface potential, topographical and electrostatic nanoscale domains. To probe these nanodomains in soft matter is a challenging task both experimentally and theoretically. This work addresses the effects of cholesterol, lipid composition, lipid charge, and lipid phase on the monolayer structure and the electrical surface potential distribution...
November 30, 2016: Soft Matter
https://www.readbyqxmd.com/read/27889577/brain-uptake-and-metabolism-of-the-endocannabinoid-anandamide-labeled-in-either-the-arachidonoyl-or-ethanolamine-moiety
#5
Kun Hu, Shilpa Sonti, Sherrye T Glaser, Richard I Duclos, Samuel J Gatley
INTRODUCTION: Anandamide (N-arachidonoylethanolamine) is a retrograde neuromodulator that activates cannabinoid receptors. The concentration of anandamide in the brain is controlled by fatty acid amide hydrolase (FAAH), which has been the focus of recent drug discovery efforts. Previous studies in C57BL/6 mice using [(3)H-arachidonoyl]anandamide demonstrated deposition of tritium in thalamus and cortical areas that was blocked by treatment with an FAAH inhibitor and that was not seen in FAAH-knockout mice...
November 9, 2016: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/27888074/toxoplasma-gondii-immune-mapped-protein-1-is-anchored-to-the-inner-leaflet-of-the-plasma-membrane-and-adopts-a-novel-protein-fold
#6
Yonggen Jia, Stefi Benjamin, Qun Liu, Yingqi Xu, Sunil Kumar Dogga, Jing Liu, Stephen Matthews, Dominique Soldati-Favre
The immune mapped protein 1 (IMP1) was first identified as a protective antigen in Eimeria maxima and described as vaccine candidate and invasion factor in Toxoplasma gondii. We show here that TgIMP1 localizes to the inner leaflet of plasma membrane (PM) via dual acylation. Mutations either in the N-terminal myristoylation or palmitoylation sites (G2 and C5) cause relocalization of TgIMP1 to the cytosol. The first 11 amino acids are sufficient for PM targeting and the presence of lysine (K7) is critical. Disruption of TgIMP1 gene by double homologous recombination revealed no invasion defect or any measurable alteration in the lytic cycle of tachyzoites...
November 22, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27885627/enzyme-complexes-important-for-the-glutamate-glutamine-cycle
#7
Mary C McKenna, Gustavo C Ferreira
Transient multienzyme and/or multiprotein complexes (metabolons) direct substrates toward specific pathways and can significantly influence the metabolism of glutamate and glutamine in the brain. Glutamate is the primary excitatory neurotransmitter in brain. This neurotransmitter has essential roles in normal brain function including learning and memory. Metabolism of glutamate involves the coordinated activity of astrocytes and neurons and high affinity transporter proteins that are selectively distributed on these cells...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27882739/familial-acute-necrotizing-encephalopathy-without-ranbp2-mutation-poor-outcome
#8
Naoko Nishimura, Yoshihisa Higuchi, Nobusuke Kimura, Fumihito Nozaki, Tomohiro Kumada, Ai Hoshino, Makiko Saitoh, Masashi Mizuguchi
Most childhood cases of acute necrotizing encephalopathy (ANE) involve neither family history nor recurrence. ANE occasionally occurs, however, as a familial disorder or recurs in Caucasian patients. A mutation of RAN-binding protein 2 (RANBP2) has been discovered in more than one half of familial or recurrent ANE patients. In contrast, there has been no report of this mutation in East Asia. Here, we report the first sibling cases of typical ANE in Japan, with poor outcome. DNA analysis of genes associated with ANE or other encephalopathies, including RANBP2 and carnitine palmitoyl transferase II (CPT2), indicated neither mutations nor disease-related polymorphisms...
November 2016: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/27879337/interactions-between-melanin-enzymes-and-their-atypical-recruitment-to-the-secretory-pathway-by-palmitoylation
#9
Srijana Upadhyay, Xinping Xu, Xiaorong Lin
: Melanins are biopolymers that confer coloration and protection to the host organism against biotic or abiotic insults. The level of protection offered by melanin depends on its biosynthesis and its subcellular localization. Previously, we discovered that Aspergillus fumigatus compartmentalizes melanization in endosomes by recruiting all melanin enzymes to the secretory pathway. Surprisingly, although two laccases involved in the late steps of melanization are conventional secretory proteins, the four enzymes involved in the early steps of melanization lack a signal peptide or a transmembrane domain and are thus considered "atypical" secretory proteins...
November 22, 2016: MBio
https://www.readbyqxmd.com/read/27875558/palmitoylated-app-forms-dimers-cleaved-by-bace1
#10
Raja Bhattacharyya, Rebecca H Fenn, Cory Barren, Rudolph E Tanzi, Dora M Kovacs
A major rate-limiting step for Aβ generation and deposition in Alzheimer's disease brains is BACE1-mediated cleavage (β-cleavage) of the amyloid precursor protein (APP). We previously reported that APP undergoes palmitoylation at two cysteine residues (Cys186 and Cys187) in the E1-ectodomain. 8-10% of total APP is palmitoylated in vitro and in vivo. Palmitoylated APP (palAPP) shows greater preference for β-cleavage than total APP in detergent resistant lipid rafts. Protein palmitoylation is known to promote protein dimerization...
2016: PloS One
https://www.readbyqxmd.com/read/27875292/dissociation-of-golgi-associated-dhhc-type-zinc-finger-protein-godz-and-sertoli-cell-gene-with-a-zinc-finger-domain-%C3%AE-serz-%C3%AE-mediated-palmitoylation-by-loss-of-function-analyses-in-knockout-mice
#11
Casey L Kilpatrick, Shoko Murakami, Mengyang Feng, Xia Wu, Rachnanjali Lal, Gong Chen, Keyong Du, Bernhard Luscher
The γ2 subunit of GABA-A receptors (GABAARs) is thought to be subject to palmitoylation by both, Golgi-associated DHHC-type zinc finger protein (GODZ, also known as DHHC3) and its paralog, Sertoli cell gene with a Zinc finger domain-β (SERZ-β, DHHC7) based on overexpression of enzymes and substrates in heterologous cells. We here have further investigated the substrate specificity of these enzymes by characterization of GODZ and SERZ-β knockout (KO) mice as well as double KO (DKO) neurons. Palmitoylation of γ2 and a second substrate, growth associated protein 43 (GAP-43) that is independently implicated in trafficking of GABAARs, was significantly reduced in brain of GODZ KO vs...
November 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27874097/molecular-insight-into-affinities-of-gallated-and-nongallated-proanthocyanidins-dimers-to-lipid-bilayers
#12
Wei Zhu, Le Xiong, Jinming Peng, Xiangyi Deng, Jun Gao, Chun-Mei Li
Experimental studies have proved the beneficial effects of proanthocyanidins (Pas) relating to interaction with the cell membrane. But the detailed mechanisms and structure-function relationship was unclear. In present study, molecular dynamics (MD) simulations were used to study the interactions of four PA dimers with a lipid bilayer composed of 1:1 mixed 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC) and 1-palmitoyl-2-oleoyl phosphatidylethanolamine (POPE). The results showed that the gallated PA dimers had much higher affinities to the bilayer with lower binding free energies compared with nongallated PA dimers...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27872144/cytotoxic-1-deoxysphingolipids-are-metabolized-by-a-cytochrome-p450-dependent-pathway
#13
Irina Alecu, Alaa Othman, Anke Penno, Essa M Saied, Christoph Arenz, Arnold von Eckardstein, Thorsten Hornemann
1-Deoxysphingolipids (1-deoxySLs) are atypical sphingolipids which are formed when serine palmitoyltransferase condenses palmitoyl-CoA with alanine instead of serine during sphingolipid synthesis. 1-DeoxySLs are toxic to neurons and pancreatic beta-cells. Pathologically elevated 1-deoxySLs cause the inherited neuropathy HSAN1 and are also found in type 2 diabetes. Diabetic sensory polyneuropathy and HSAN1 are clinically very similar, suggesting that 1-deoxySLs may be implicated in both pathologies. 1-DeoxySLs are considered to be dead-end metabolites, as they lack the C1-hydroxyl group which is essential for the canonical degradation of sphingolipids...
November 21, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27862466/role-of-ammonium-in-the-ionization-of-phosphatidylcholines-during-electrospray-mass-spectrometry
#14
Michael D Rush, Richard B van Breemen
RATIONALE: Electrospray mass spectrometry methods for the analysis of phosphatidylcholines (PCs) routinely include ammonium acetate or ammonium formate in the mobile phase. In an effort to justify and optimize the use of these additives, we investigated possible functions of ammonium compounds in the ionization of PCs. METHODS: Because PCs contain a quaternary amine, the role of ammonium in neutralizing the negatively charged phosphate group was investigated by using deuterated ammonium acetate, adjusting the pH, varying the organic solvent composition, and by comparing the additives ammonium acetate, ammonium formate and ammonium bicarbonate...
November 11, 2016: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/27859784/membrane-skeletal-association-and-post-translational-allosteric-regulation-of-toxoplasma-gondii-gapdh1
#15
Rashmi Dubey, Bart L Staker, Ian T Foe, Matthew Bogyo, Peter J Myler, Huân M Ngô, Marc-Jan Gubbels
When Toxoplasma gondii egresses from the host cell, glyceraldehyde-3-phosphate dehydrogenase 1 (GAPDH1), which is primary a glycolysis enzyme but actually a quintessential multifunctional protein, translocates to the unique cortical membrane skeleton. Here we report the 2.25Å resolution crystal structure of the GAPDH1 holoenzyme in a quaternary complex providing the basis for the molecular dissection of GAPDH1 structure-function relationships Knockdown of GAPDH1 expression and catalytic site disruption validate the essentiality of GAPDH1 in intracellular replication but we confirmed that glycolysis is not strictly essential...
November 17, 2016: Molecular Microbiology
https://www.readbyqxmd.com/read/27854029/acute-administration-of-3-5-diiodo-l-thyronine-to-hypothyroid-rats-stimulates-bioenergetic-parameters-in-liver-mitochondria
#16
Alessandro Cavallo, Federica Taurino, Fabrizio Damiano, Luisa Siculella, Anna Maria Sardanelli, Antonio Gnoni
The role of 3,5-diiodo-L-thyronine (T2), initially considered only a 3,3',5-triiodo-L-thyronine (T3) catabolite, in the bioenergetic metabolism is of growing interest. In this study we investigated the acute effects (within 1 h) of T2 administration to hypothyroid rats on liver mitochondria fatty acid uptake and β-oxidation rate, mitochondrial efficiency (by measuring proton leak) and mitochondrial oxidative damage (by determining H2O2 release). Fatty acid uptake into mitochondria was measured assaying carnitine palmitoyl transferase (CPT) I and II activities, and fatty acid β-oxidation using palmitoyl-CoA as a respiratory substrate...
November 17, 2016: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/27852864/palmitoylation-of-sindbis-virus-tf-protein-regulates-its-plasma-membrane-localization-and-subsequent-incorporation-into-virions
#17
Jolene Ramsey, Emily C Renzi, Randy J Arnold, Jonathan C Trinidad, Suchetana Mukhopadhyay
: Palmitoylation is a reversible, post-translational modification that helps target proteins to cellular membranes. The alphavirus small membrane proteins 6K and TF have been reported to be palmitoylated and to positively regulate budding. 6K and TF are isoforms identical in the N-terminus but unique in the C-terminus due to a (-1) ribosomal frameshift during translation. In this study we used cysteine (Cys) mutants to test differential palmitoylation of Sindbis virus 6K and TF proteins...
November 16, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27851939/-2-h-nmr-and-md-simulations-reveal-membrane-bound-conformation-of-magainin-2-and-its-synergy-with-pgla
#18
Erik Strandberg, Diana Horn, Sabine Reißer, Jonathan Zerweck, Parvesh Wadhwani, Anne S Ulrich
Magainin 2 (MAG2) and PGLa are two α-helical antimicrobial peptides found in the skin of the African frog Xenopus laevis. They act by permeabilizing bacterial membranes and exhibit an exemplary synergism. Here, we determined the detailed molecular alignment and dynamical behavior of MAG2 in oriented lipid bilayers by using (2)H-NMR on Ala-d3-labeled peptides, which yielded orientation-dependent quadrupolar splittings of the labels. The amphiphilic MAG2 helix was found to lie flat on the membrane surface in 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC)/1,2-dimyristoyl-sn-glycero-3-phosphatidylglycerol (DMPG) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC)/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylglycerol (POPG), as expected, with a tilt angle close to 90°...
November 15, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27848929/the-role-of-a-conserved-membrane-proximal-cysteine-in-altering-%C3%AE-ps2c%C3%AE-ps-integrin-diffusion
#19
Aleem Syed, Neha Arora, Thomas A Bunch, Emily A Smith
Cysteine residues (Cys) in the membrane proximal region are common post-translational modification (PTM) sites in transmembrane proteins. Herein, the effects of a highly conserved membrane proximal α-subunit Cys(1368) on the diffusion properties of αPS2CβPS integrins are reported. Sequence alignment shows that this cysteine is palmitoylated in human α3 and α6 integrin subunits. Replacing Cys(1368) in wild-type integrins with valine (Val(1368)) putatively blocks a PTM site and alters integrins' ligand binding and diffusion characteristics...
November 15, 2016: Physical Biology
https://www.readbyqxmd.com/read/27845924/temperature-dependent-heterogeneous-rotational-correlation-in-lipids
#20
Neda Dadashvand, Christina M Othon
Lipid structures exhibit complex and highly dynamic lateral structure; and changes in lipid density and fluidity are believed to play an essential role in membrane targeting and function. The dynamic structure of liquids on the molecular scale can exhibit complex transient density fluctuations. Here the lateral heterogeneity of lipid dynamics is explored in free standing lipid monolayers. As the temperature is lowered the probes exhibit increasingly broad and heterogeneous rotational correlation. This increase in heterogeneity appears to exhibit a critical onset, similar to those observed for glass forming fluids...
November 15, 2016: Physical Biology
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