AfTMEM16/nanodisc complex in the presence of Ca2+ and 5mol% Ceramide 24:0
Ontology highlight
ABSTRACT:
SUBMITTER: Alessio Accardi
PROVIDER: EMPIAR-10240 | biostudies-other |
REPOSITORIES: biostudies-other
Similar Datasets
Project description: Not available
| EMPIAR-10239 | biostudies-other
Project description: Not available
| EMPIAR-10241 | biostudies-other
Project description:Ceramide-1-phosphate, the phosphorylated form of ceramide, gained attention recently due to its diverse intracellular roles, in particular in inflammation mediated by cPLA(2)alpha. However, surprisingly little is known about the physical chemical properties of this lipid and its potential impact on physiological function. For example, the presence of Ca(2+) is indispensable for the interaction of Cer-1-P with the C2 domain of cPLA(2)alpha. We report on the structure and morphology of Cer-1-P in monomolecular layers at the air/water solution interface in the absence and presence of Ca(2+) using diverse biophysical techniques, including synchrotron x-ray reflectivity and grazing angle diffraction, to gain insight into the role and function of Cer-1-P in biomembranes. We show that relatively small changes in pH and the presence of monovalent cations dramatically affect the behavior of Cer-1-P. On pure water Cer-1-P forms a solid monolayer despite the negative charge of the phosphomonoester headgroup. In contrast, pH 7.2 buffer yields a considerably less solid-like monolayer, indicating that charge-charge repulsion becomes important at higher pH. Calcium was found to bind strongly to the headgroup of Cer-1-P even in the presence of a 100-fold larger Na(+) concentration. Analysis of the x-ray reflectivity data allowed us to estimate how much Ca(2+) is bound to the headgroup, approximately 0.5 Ca(2+) and approximately 1.0 Ca(2+) ions per Cer-1-P molecule for the water and buffer subphase respectively. These results can be qualitatively understood based on the molecular structure of Cer-1-P and the electrostatic/hydrogen-bond interactions of its phosphomonoester headgroup. Biological implications of our results are also discussed.
| S-EPMC2717294 | biostudies-literature
Project description:ObjectiveTotal ceramide concentrations are linked with increased insulin resistance and cardiac dysfunction. However, recent studies have demonstrated that plasma concentrations of specific very-long-chain fatty ceramides (C24:0 and C22:0) are associated with a reduced incidence of coronary heart disease and all-cause mortality. We hypothesized that specific genetic loci are associated with plasma C22:0 and C24:0 concentrations.MethodsHeritability and genome-wide association studies of plasma C24:0 and C22:0 ceramide concentrations were performed among 2,217 participants in the Framingham Heart Study Offspring Cohort, adjusting for cardiovascular risk factor covariates and cardiovascular drug treatment.ResultsThe multivariable-adjusted heritability for C22:0 and C24:0 ceramides was 0.42 (standard error [SE], 0.07; p=1.8E-9) and 0.25 (SE, 0.08; p=0.00025), respectively. Nineteen single nucleotide polymorphisms (SNPs), all on chromosome 20, significantly associated with C22:0 concentrations; the closest gene to these variants was SPTLC3. The lead SNP (rs4814175) significantly associated with 3% lower plasma C22:0 concentrations (p=2.83E-11). Nine SNPs, all on chromosome 20 and close to SPTLC3, were significantly associated with C24:0 ceramide concentrations. All 9 were also significantly related to plasma C22:0 levels. The lead SNP (rs168622) was significantly associated with 10% lower plasma C24:0 ceramide concentrations (p=9.94E-09).ConclusionSNPs near the SPTLC3 gene, which encodes serine palmitoyltransferase long chain base subunit 3 (SPTLC3; part of the enzyme that catalyzes the rate-limiting step of de novo sphingolipid synthesis) were associated with plasma C22:0 and C24:0 ceramide concentrations. These results are biologically plausible and suggest that SPTLC3 may be a potential therapeutic target for C24:0 and C22:0 ceramide modulation.
| S-EPMC7266332 | biostudies-literature
Project description:Global positioning systems (GPS) have recently been shown to reliably quantify the spatiotemporal characteristics of Polo, with the physiological demands of Polo play at low- and high-goal levels also investigated. This study aims to describe the spatiotemporal demands of Polo across 0-24 goal levels. A player-worn GPS unit was used to quantify distance, speed and high-intensity activities performed. Data were divided into chukkas and five equine-based speed zones, grouped per cumulative player handicap and assessed using standardized mean differences. Average distance and speed per chukka increased in accordance with cumulative player handicap, with the magnitude of differences being trivial-large and trivial-very large, respectively. Differences between time spent in high-intensity speed zones (zones 4 and 5) show a linear increase in magnitude, when comparing 0 goal Polo to all other levels of play (Small-Very Large; 6-24 goals, respectively). High-intensity activities predominantly shared this trend, displaying trivial-large differences between levels. These findings highlight increased cardiovascular, anaerobic and speed based physiological demands on Polo ponies as playing level increases. Strategies such as high-intensity interval training, maximal speed work and aerobic conditioning may be warranted to facilitate this development and improve pony welfare and performance.
| S-EPMC6680633 | biostudies-literature
Project description:The title compound, C(43)H(45)NO(12), was prepared from the reaction of 2,6-bis-(dibromo-meth-yl)pyridine and bis-phenol in the presence of caesium carbonate as a base. The central ring makes dihedral angles of 64.83 (6), 13.48 (6), 56.96 (6) and 66.21 (6)° with the peripheral rings. In the crystal, mol-ecules are linked by weak C-H⋯O and C-H⋯π inter-actions, forming a folded structure.
| S-EPMC3470260 | biostudies-literature
Project description:Sphingolipids are structural membrane components that also function in cellular stress responses. The serine palmitoyltransferase (SPT) catalyzes the rate-limiting step in sphingolipid biogenesis. Its activity is tightly regulated through multiple binding partners, including Tsc3, Orm proteins, ceramides, and the phosphatidylinositol-4-phosphate (PI4P) phosphatase Sac1. The structural organization and regulatory mechanisms of this complex are not yet understood. Here, we report the high-resolution cryo-EM structures of the yeast SPT in complex with Tsc3 and Orm1 (SPOT) as dimers and monomers and a monomeric complex further carrying Sac1 (SPOTS). In all complexes, the tight interaction of the downstream metabolite ceramide and Orm1 reveals the ceramide-dependent inhibition. Additionally, observation of ceramide and ergosterol binding suggests a co-regulation of sphingolipid biogenesis and sterol metabolism within the SPOTS complex.
| S-EPMC10550967 | biostudies-literature
Project description:After activation by an agonist, G-protein-coupled receptors (GPCRs) recruit β-arrestin, which desensitizes heterotrimeric G-protein signalling and promotes receptor endocytosis1. Additionally, β-arrestin directly regulates many cell signalling pathways that can induce cellular responses distinct from that of G proteins2. In contrast to G proteins, for which there are many high-resolution structures in complex with GPCRs, the molecular mechanisms underlying the interaction of β-arrestin with GPCRs are much less understood. Here we present a cryo-electron microscopy structure of β-arrestin 1 (βarr1) in complex with M2 muscarinic receptor (M2R) reconstituted in lipid nanodiscs. The M2R-βarr1 complex displays a multimodal network of flexible interactions, including binding of the N domain of βarr1 to phosphorylated receptor residues and insertion of the finger loop of βarr1 into the M2R seven-transmembrane bundle, which adopts a conformation similar to that in the M2R-heterotrimeric Go protein complex3. Moreover, the cryo-electron microscopy map reveals that the C-edge of βarr1 engages the lipid bilayer. Through atomistic simulations and biophysical, biochemical and cellular assays, we show that the C-edge is critical for stable complex formation, βarr1 recruitment, receptor internalization, and desensitization of G-protein activation. Taken together, these data suggest that the cooperative interactions of β-arrestin with both the receptor and the phospholipid bilayer contribute to its functional versatility.
| S-EPMC7367492 | biostudies-literature
Project description:Four dye swap replicates were performed with material derived 24 hours after stimulation of HUVECs with PMA and RMAC11 hybridised to material obtained at time 0 hours. The cDNAs used in this microarray were identified as part of collaborative project between the IMVS and Bionomics Limited. The project aims were to identify genes up-regulated during in vitro capillary tube formation as targets for angiogenesis-based therapeutics. Any requests for further information regarding the data generated from this collaboration should be directed to Bionomics Limited (www.bionomics.com.au) at the following address: Bionomics Limited 31 Dalgleish Street Thebarton, South Australia Australia, 5031 Phone: 618 8354 6104 Fax: 618 8354 6199 Email: busdev@bionomics.com.au Keywords = angiogenesis Keywords = HUVEC Keywords = in vitro Keywords = capillary tube Keywords: repeat sample
2003-11-25 | GSE778 | GEO
Project description:Cutaneous T cell lymphomas (CTCLs) represent a heterogeneous group of T cell lymphomas that primarily affect the skin. The most frequent forms of CTCL are mycosis fungoides and Sézary syndrome. Both are characterized by frequent recurrence, developing chronic conditions and high mortality with a lack of a curative treatment. In this study, we evaluated the effect of short-chain, cell-permeable C6 Ceramide (C6Cer) on CTCL cell lines and keratinocytes. C6Cer significantly reduced cell viability of CTCL cell lines and induced cell death via apoptosis and necrosis. In contrast, primary human keratinocytes and HaCaT keratinocytes were less affected by C6Cer. Both keratinocyte cell lines showed higher expressions of ceramide catabolizing enzymes and HaCaT keratinocytes were able to metabolize C6Cer faster and more efficiently than CTCL cell lines, which might explain the observed protective effects. Along with other existing skin-directed therapies, C6Cer could be a novel well-tolerated drug for the topical treatment of CTCL.
| S-EPMC7828274 | biostudies-literature