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991.
Hakobyan S Harris CL van den Berg CW Fernandez-Alonso MC de Jorge EG de Cordoba SR Rivas G Mangione P Pepys MB Morgan BP 《The Journal of biological chemistry》2008,283(45):30451-30460
Binding of the complement regulatory protein, factor H, to C-reactive protein has been reported and implicated as the biological basis for association of the H402 polymorphic variant of factor H with macular degeneration. Published studies utilize solid-phase or fluid-phase binding assays to show that the factor H Y402 variant binds C-reactive protein more strongly than H402. Diminished binding of H402 variant to C-reactive protein in retinal drusen is posited to permit increased complement activation, driving inflammation and pathology. We used well validated native human C-reactive protein and pure factor H Y402H variants to test interactions. When factor H variants were incubated with C-reactive protein in the fluid phase at physiological concentrations, no association occurred. When C-reactive protein was immobilized on plastic, either non-specifically by adsorption in the presence of Ca(2+) to maintain its native fold and pentameric subunit assembly or by specific Ca(2+)-dependent binding to immobilized natural ligands, no specific binding of either factor H variant from the fluid phase was observed. In contrast, both factor H variants reproducibly bound to C-reactive protein immobilized in the absence of Ca(2+), conditions that destabilize the native fold and pentameric assembly. Both factor H variants strongly bound C-reactive protein that was denatured by heat treatment before immobilization, confirming interaction with denatured but not native C-reactive protein. We conclude that the reported binding of factor H to C-reactive protein results from denaturation of the C-reactive protein during immobilization. Differential binding to C-reactive protein, thus, does not explain association of the Y402H polymorphism with macular degeneration. 相似文献
992.
The reticulon and DP1/Yop1p proteins form immobile oligomers in the tubular endoplasmic reticulum 总被引:2,自引:0,他引:2
Shibata Y Voss C Rist JM Hu J Rapoport TA Prinz WA Voeltz GK 《The Journal of biological chemistry》2008,283(27):18892-18904
We recently identified a class of membrane proteins, the reticulons and DP1/Yop1p, which shape the tubular endoplasmic reticulum (ER) in yeast and mammalian cells. These proteins are highly enriched in the tubular portions of the ER and virtually excluded from other regions. To understand how they promote tubule formation, we characterized their behavior in cellular membranes and addressed how their localization in the ER is determined. Using fluorescence recovery after photobleaching, we found that yeast Rtn1p and Yop1p are less mobile in the membrane than normal ER proteins. Sucrose gradient centrifugation and cross-linking analyses show that they form oligomers. Mutants of yeast Rtn1p, which no longer localize exclusively to the tubular ER or are even totally inactive in inducing ER tubules, are more mobile and oligomerize less extensively. The mammalian reticulons and DP1 are also relatively immobile and can form oligomers. The conserved reticulon homology domain that includes the two membrane-embedded segments is sufficient for the localization of the reticulons to the tubular ER, as well as for their diffusional immobility and oligomerization. Finally, ATP depletion in both yeast and mammalian cells further decreases the mobilities of the reticulons and DP1. We propose that oligomerization of the reticulons and DP1/Yop1p is important for both their localization to the tubular domains of the ER and for their ability to form tubules. 相似文献
993.
Rutkowska A Mayer MP Hoffmann A Merz F Zachmann-Brand B Schaffitzel C Ban N Deuerling E Bukau B 《The Journal of biological chemistry》2008,283(7):4124-4132
In all organisms ribosome-associated chaperones assist early steps of protein folding. To elucidate the mechanism of their action, we determined the kinetics of individual steps of the ribosome binding/release cycle of bacterial trigger factor (TF), using fluorescently labeled chaperone and ribosome-nascent chain complexes. Both the association and dissociation rates of TF-ribosome complexes are modulated by nascent chains, whereby their length, sequence, and folding status are influencing parameters. However, the effect of the folding status is modest, indicating that TF can bind small globular domains and accommodate them within its substrate binding cavity. In general, the presence of a nascent chain causes an up to 9-fold increase in the rate of TF association, which provides a kinetic explanation for the observed ability of TF to efficiently compete with other cytosolic chaperones for binding to nascent chains. Furthermore, a subset of longer nascent polypeptides promotes the stabilization of TF-ribosome complexes, which increases the half-life of these complexes from 15 to 50 s. Nascent chains thus regulate their folding environment generated by ribosome-associated chaperones. 相似文献
994.
The synthetic peptide identical to the C-terminus of murine S100A9 protein (mS100A9p) has antinociceptive effect on different acute inflammatory pain models. In this study, the effect of mS100A9p was investigated on neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve in rats. Hyperalgesia, allodynia, and spontaneous pain were assessed to evaluate nociception. These three signs were detected as early as 2 days after sciatic nerve constriction and lasted for over 14 days after CCI. Rats were treated with different doses of mS100A9p by intraplantar, oral, or intrathecal routes on day 14 after CCI, and nociception was evaluated 1h later. These three routes of administration blocked hyperalgesia, allodynia and spontaneous pain. The duration of the effect of mS100A9p depends on the route used and phenomenon analyzed. Moreover, intraplantar injection of mS100A9p in the contralateral paw inhibited the hyperalgesia on day 14 days after CCI. The results obtained herein demonstrate the antinociceptive effect of the C-terminus of murine S100A9 protein on experimental neuropathic pain, suggesting a potential therapeutic use for it in persistent pain syndromes, assuming that tolerance does not develop to mS100A9p. 相似文献
995.
Pivneva T Haas B Reyes-Haro D Laube G Veh RW Nolte C Skibo G Kettenmann H 《Cell calcium》2008,43(6):591-601
Ca(2+) signaling is the astrocyte form of excitability and the endoplasmic reticulum (ER) plays an important role as an intracellular Ca(2+) store. Since the subcellular distribution of the ER influences Ca(2+) signaling, we compared the arrangement of ER in astrocytes of hippocampus tissue and astrocytes in cell culture by electron microscopy. While the ER was usually located in close apposition to the plasma membrane in astrocytes in situ, the ER in cultured astrocytes was close to the nuclear membrane. Activation of metabotropic receptors linked to release of Ca(2+) from ER stores triggered distinct responses in cultured and in situ astrocytes. In culture, Ca(2+) signals were commonly first recorded close to the nucleus and with a delay at peripheral regions of the cells. Store-operated Ca(2+) entry (SOC) as a route to refill the Ca(2+) stores could be easily identified in cultured astrocytes as the Zn(2+)-sensitive component of the Ca(2+) signal. In contrast, such a Zn(2+)-sensitive component was not recorded in astrocytes from hippocampal slices despite of evidence for SOC. Our data indicate that both, astrocytes in situ and in vitro express SOC necessary to refill stores, but that a SOC-related signal is not recorded in the cytoplasm of astrocytes in situ since the stores are close to the plasma membrane and the refill does not affect cytoplasmic Ca(2+) levels. 相似文献
996.
Influence of bacteria and salinity on diatom biogenic silica dissolution in estuarine systems 总被引:3,自引:0,他引:3
Dissolution of diatom biogenic silica (bSiO2) in estuaries and its control by water salinity and bacteria were investigated using the river euryhaline species Cyclotella meneghiniana as a model. Laboratory-controlled bioassays conducted at different salinities with an estuarine bacteria inoculum showed
a faster dissolution of diatom bSiO2 at the lowest salinity where bacteria were the most abundant. However in another experiment, salinity increase clearly enhanced
the dissolution of cleaned frustules (organic matter free). The presence of active bacteria might therefore predominate on
the effect of salinity for freshly lysed diatoms whereas salinity might rather control dissolution of organic-matter-free
frustule remains. Incubation of cultivated diatoms at different protease concentrations revealed that high proteolytic activities
had little effect on bSiO2 dissolution at a 1-month scale in spite of an efficient removal of organic matter from the frustules. Altogether it is hypothesized
that bacterial colonization increases bSiO2 dissolution by creating a microenvironment at the diatom surface with high ectoproteolytic activity but also via the release
of metabolic byproducts since the presence of organic matter seems generally to facilitate diatom bSiO2 dissolution. 相似文献
997.
Germ line control of female sex determination in zebrafish 总被引:2,自引:0,他引:2
A major transition during development of the gonad is commitment from an undifferentiated “bi-potential” state to ovary or testis fate. In mammals, the oogonia of the developing ovary are known to be important for folliculogenesis. An additional role in promoting ovary fate or female sex determination has been suggested, however it remains unclear how the germ line might regulate this process. Here we show that the germ line is required for the ovary versus testis fate choice in zebrafish. When the germ line is absent, the gonad adopts testis fate. These germ line deficient testes have normal somatic structures indicating that the germ line influences fate determination of surrounding somatic tissues. In germ line deficient animals the expression of the ovary specific gene cyp19a1a fails to be maintained whereas the testis genes sox9a and amh remain expressed. Furthermore, we observed decreased levels of the ovary specific genes cyp19a1a and foxL2 in germ line deficient animals prior to morphological sex differentiation of the gonad. We propose that the germ line has a common role in female sex determination in fish and mammals. Additionally, we show that testis specification is sufficient for masculinization of the fish pointing to a direct role of hormone signaling from the gonad in directing sex differentiation of non-gonadal tissues. 相似文献
998.
Arsenic trioxide stimulates SUMO-2/3 modification leading to RNF4-dependent proteolytic targeting of PML 总被引:2,自引:0,他引:2
Weisshaar SR Keusekotten K Krause A Horst C Springer HM Göttsche K Dohmen RJ Praefcke GJ 《FEBS letters》2008,582(21-22):3174-3178
We have recently reported that poly-SUMO-2/3 conjugates are subject to a ubiquitin-dependent proteolytic control in human cells. Here we show that arsenic trioxide (ATO) increases SUMO-2/3 modification of promyelocytic leukemia (PML) leading to its subsequent ubiquitylation in vivo. The SUMO-binding ubiquitin ligase RNF4 mediates this modification and causes disruption of PML nuclear bodies upon treatment with ATO. Reconstitution of SUMO-dependent ubiquitylation of PML by RNF4 in vitro and in a yeast trans vivo system revealed a preference of RNF4 for chain forming SUMOs. Polysumoylation of PML in response to ATO thus leads to its recognition and ubiquitylation by RNF4. 相似文献
999.
The repetitive [RTRG](6) peptide was fortuitously identified as a potent nuclear localization signal when linked to the green fluorescent reporter protein. Replacing the arginines by lysines, or the threonines by glycines, both resulted in a decreased nuclear targeting ability of the peptide within this context. By contrast, the sequence [RT](12) proved able to drive nuclear accumulation of the linked protein as efficiently as the starting peptide. Remarkably, [RTRG](n) peptides where n=2 to 6 showed a gradual, copy-number dependent, increase in their ability to target the green fluorescent protein to the cell nucleus. As a consequence, the nuclear to cytoplasmic concentration ratio of the linked protein within the cell could be adjusted to different values depending on the number of repeats used in the fusion. Our observation may open the way to the use of [RTRG](n) repeats of given lengths (n=2 to 6) for fixing the nuclear-cytoplasmic partition of shuttling protein domains in the course of their functional study. 相似文献
1000.
Transpiration and photosynthesis of current-year stems and adult leaves of different deciduous tree species were investigated
to estimate their probable influence on carbon balance. Peridermal transpiration of young stems was found to be rather small
as compared to the transpiration of leaves (stem/leaf like 1/5–1/20). A characteristic that was mainly attributable to the
lower peridermal conductance to water and CO2, which made up only 8–28% of stomatal conductance. Water vapour conductance was significantly lower in stems, but also non-responsive
to PAR, which led to a comparatively higher water use efficiency (WUE, ratio assimilation/transpiration). Thus, although corticular
photosynthesis reached only 11–37% of leaf photosynthesis, it may be a means of improving the carbon balance of stems under
limited water availability. The influence of drought stress on primary photosynthetic reactions was also studied. Under simulated
drought conditions the drying time needed to provoke a 50% reduction (t
50) in dark- and light-adapted PSII efficiency (Fv/Fm, ΔF/Fm′) was up to ten times higher in stems than in leaves. Nevertheless,
up to a relative water deficit (RWD) of around 40–50% dark-adapted PSII efficiency of leaves and stems was rather insensitive
to dehydration, showing that the efficiency of open PS II reaction centres is not impaired. Thus, it may be concluded that
in stems as well as in leaves the primary site of drought damage is at the level of dark enzyme reactions and not within PSII.
However, enduring severe drought caused photoinhibitory damage to the photosynthetic apparatus of leaves and stems; thereby
RWD50 values (= RWD needed to provoke a 50% reduction in Fv/Fm ad ΔF/Fm′) were comparably lower in stems as compared to leaves,
indicating a possibly higher drought sensitivity of the cortex chlorenchyma. 相似文献