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Molecular dynamics (MD) simulations of phosphatidylinositol (4,5)-bisphosphate (PIP2) and phosphatidylinositol (3,4,5)-trisphosphate (PIP3) in 1-palmitoyl 2-oleoyl phosphatidylcholine (POPC) bilayers indicate that the inositol rings are tilted ∼40° with respect to the bilayer surface, as compared with 17° for the P-N vector of POPC. Multiple minima were obtained for the ring twist (analogous to roll for an airplane). The phosphates at position 1 of PIP2 and PIP3 are within an Ångström of the plane formed by the phosphates of POPC; lipids in the surrounding shell are depressed by 0.5-0.8 Å, but otherwise the phosphoinositides do not substantially perturb the bilayer. Finite size artifacts for ion distributions are apparent for systems of ∼26 waters/lipid, but, based on simulations with a fourfold increase of the aqueous phase, the phosphoinositide positions and orientations do not show significant size effects. Electrostatic potentials evaluated from Poisson-Boltzmann (PB) calculations show a strong dependence of potential height and ring orientation, with the maxima on the −25 mV surfaces (17.1 ± 0.1 Å for PIP2 and 19.4 ± 0.3 Å for PIP3) occurring near the most populated orientations from MD. These surfaces are well above the background height of 10 Å estimated for negatively charged cell membranes, as would be expected for lipids involved in cellular signaling. PB calculations on microscopically flat bilayers yield similar maxima as the MD-based (microscopically rough) systems, but show less fine structure and do not clearly indicate the most probable regions. Electrostatic free energies of interaction with pentalysine are also similar for the rough and flat systems. These results support the utility of a rigid/flat bilayer model for PB-based studies of PIP2 and PIP3 as long as the orientations are judiciously chosen. 相似文献
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zge Karayel Francesca Tonelli Sebastian Virreira Winter Phillip E. Geyer Ying Fan Esther M. Sammler Dario R. Alessi Martin Steger Matthias Mann 《Molecular & cellular proteomics : MCP》2020,19(9):1546-1560
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- •MS-based clinical assay that accurately determines phospho Rab10 occupancy.
- •Stable isotope labeled phosphopeptide injected as a standard with endogenous tryptic phospho Rab peptide for accurate ratio determination.
- •Determination of pRab levels in neutrophils of Parkinson disease patients.
- •Relevance of pRab levels as marker of PD.
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Food subsidies have the potential to modify ecosystems and affect the provision of goods and services. Predictable Anthropogenic Food Subsidies (PAFS) modify ecosystems by altering ecological processes and food webs. The global concern over the effects of PAFS in ecosystems has led to development of environmental policies aimed at curbing the production or ultimately banning of PAFS. However, the effects of reducing or banning PAFS are not known. We explore the consequences of PAFS removal in a marine ecosystem under two scenarios: 1) gradual reduction, or 2) an abrupt ban, using a mass balance model to test these hypotheses–The reduction or loss of PAFS will: i) modify trophic levels and food webs through effects on foraging by opportunistic species, ii) increase the resilience of opportunistic species to food shortages, and iii) modify predator–prey interactions through shifts in prey consumption. We found that PAFS lower the trophic levels of opportunistic scavengers and increase their food pathways. Scavengers are able to switch prey when PAFS are reduced gradually but they decline when PAFS are abruptly banned. PAFS reduction to a certain minimal level causes a drop in the ecosystem’s stability. We recommend gradual reduction of PAFS to a minimal level that would maintain the ecosystem’s stability and allow species exploiting PAFS to habituate to the food subsidy reduction. 相似文献
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John H. Nordin Esther L. Beaudoin Xiaodong Liu 《Archives of insect biochemistry and physiology》1990,15(3):119-135
In the eggs of the cockroach Blattella germanica, vitellin (Vt) utilization is initiated 4 days postovulation by the proteolytic processing of its three subunits. These reactions yield a specific set of peptides that are consumed by the developing embryo. A yolk proteinase activity, believed central to this processing event, has been investigated. First expressed at day 3 postovulation, just prior to Vt's processing, its specific activity with synthetic substrates increased four-fold to 18-fold through day 6. In addition, a mixing experiment showed that these proteinases(s) can also process Vt's large subunits in vitro. A relationship between Vt processing and proteinase specific activity was also noted with two B. germanica translocation heterozygotes, which displayed differences in the extent of Vt processing. One group of eggs (group A) failed to process any Vt subunit. A second group (B) processed the Mr 102,000 subunit but not the Mr 95,000. A third group (C) processed their Vt normally. Proteinase specific activities in the yolk of translocant's eggs at day 6 mirrored the extent of processing, being highest in group C eggs and effectively absent from the yolk of group A eggs. Eggs defective in Vt processing also contained arrested embryos. It is concluded that the yolk proteinase activity described here participates in Vt processing at day 4 postovulation. Microscopic examination of yolk obtained from eggs of wild type females showed that, as processing began in vivo (day 4), the yolk granules also underwent an abrupt decrease in size from diameters of 15–30 μm to 3–10 μm. Yolk granules of those translocant's eggs that were defective in Vt processing did not undergo this size decrease, suggesting that granule reorganization and Vt proteolysis may be linked functionally. 相似文献
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Enzyme levels of lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured in the cytosol of renal cortex samples from either normal and pathologic kidney tissue. The mean enzyme activity values, expressed in Units per gram of cytosolic protein decreased in the following order: normal cortex (LDH = 4,299 +/- 654; AST = 522 +/- 101; ALT = 197 +/- 44). chronic pyelonephritis (LDH = 2,360 +/- 876; AST = 297 +/- 117; ALT = 90 +/- 48), hydronephrosis (LDH = 2,208 +/- 1,264; AST = 279 +/- 165; ALT = 82 +/- 61), pyonephrosis (LDH = 1,410 +/- 596; AST = 158 +/- 69; ALT = 23.4 +/- 16.4) and renal tuberculosis (LDH = 1,149 +/- 481; AST = 93 +/- 34; ALT = 5.6 +/- 2.8). The decrease in the enzyme activities paralleled tissue damage and it was shown to affect cellular functionality in relation with energy and amino acid metabolism. 相似文献