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排序方式: 共有245条查询结果,搜索用时 15 毫秒
91.
The majority of mitochondrial proteins can be imported into mitochondria following termination of their translation in the cytosol. Import of fumarase and several other proteins into mitochondria does not appear to occur post-translationally according to standard in vivo and in vitro assays. However, the nature of interaction between the translation and translocation apparatuses during import of these proteins is unknown. Therefore, a major question is whether the nascent chains of these proteins are exposed to the cytosol during import into mitochondria. We asked directly if the presequence of fumarase can be cleaved by externally added mitochondrial processing peptidase (MPP) during import, using an in vitro translation-translocation coupled reaction. The presequence of fumarase was cleaved by externally added MPP during import, indicating a lack of, or a loose physical connection between, the translation and translocation of this protein. Exchanging the authentic presequence of fumarase for that of the more efficient Su9-ATPase presequence reduced the exposure of fumarase precursors to externally added MPP en route to mitochondria. Therefore, exposure to cytosolic MPP is dependent on the presequence and not on the mature part of fumarase. On the other hand, following translation in the absence of mitochondria, the authentic fumarase presequence and that of Su9-ATPase become inaccessible to added MPP when attached to mature fumarase. Thus, folding of the mature portion of fumarase, which conceals the presequence, is the reason for its inability to be imported in classical post-translational assays. Another unique feature of fumarase is its distribution between the mitochondria and the cytosol. We show that in vivo the switch of the authentic presequence with that of Su9-ATPase caused more fumarase molecules to be localized to the mitochondria. A possible mechanism by which the cytosolic exposure, the targeting efficiency, and the subcellular distribution of fumarase are dictated by the presequence is discussed. 相似文献
92.
Cohen-Mazor M Sela S Mazor R Ilan N Vlodavsky I Rops AL van der Vlag J Cohen HI Kristal B 《American journal of physiology. Heart and circulatory physiology》2008,294(2):H651-H658
Patients on chronic hemodialysis (HD) are at high risk for developing atherosclerosis and cardiovascular complications. Heparanase, an endoglycosidase that cleaves heparan sulfate (HS) side chains of proteoglycans, is involved in extracellular matrix degradation and, as such, may be involved in the atherosclerotic lesion progression. We hypothesize that heparanase is elevated in HD patients, partly due to its release from primed circulating polymorphonuclear leukocytes (PMNLs), undergoing degranulation. Priming of PMNLs was assessed by levels of CD11b and the rate of superoxide release. Heparanase mRNA expression in PMNLs was determined by RT-PCR. PMNL and plasma levels of heparanase were determined by immunoblotting, immunofluorescence, and flow cytometry analyses. The levels of soluble HS in plasma were measured by a competition ELISA. This study shows that PMNLs isolated from HD patients have higher mRNA and protein levels of heparanase compared with normal control (NC) subjects and that heparanase levels correlate positively with PMNL priming. Plasma levels of heparanase were higher in HD patients than in NC subjects and were further elevated after the dialysis session. In addition, heparanase expression inversely correlates with plasma HS levels. A pronounced expression of heparanase was found in human atherosclerotic lesions. The increased heparanase activity in the blood of HD patients results at least in part from the degranulation of primed PMNLs and may contribute to the acceleration of the atherosclerotic process. Our findings highlight primed PMNLs as a possible source for the increased heparanase in HD patients, posing heparanase as a new risk factor for cardiovascular complications and atherosclerosis. 相似文献
93.
Molecular and Phenotypic Analysis of CaVRG4, Encoding an Essential Golgi Apparatus GDP-Mannose Transporter
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Cell surface mannan is implicated in almost every aspect of pathogenicity of Candida albicans. In Saccharomyces cerevisiae, the Vrg4 protein acts as a master regulator of mannan synthesis through its role in substrate provision. The substrate for mannosylation of proteins and lipids in the Golgi apparatus is GDP-mannose, whose lumenal transport is catalyzed by Vrg4p. This nucleotide sugar is synthesized in the cytoplasm by pathways that are highly conserved in all eukaryotes, but its lumenal transport (and hence Golgi apparatus-specific mannosylation) is a fungus-specific process. To begin to study the role of Golgi mannosylation in C. albicans, we isolated the CaVRG4 gene and analyzed the effects of loss of its function. CaVRG4 encodes a functional homologue of the S. cerevisiae GDP-mannose transporter. CaVrg4p localized to punctate spots within the cytoplasm of C. albicans in a pattern reminiscent of localization of Vrg4p in the Golgi apparatus in S. cerevisiae. Like partial loss of ScVRG4 function, partial loss of CaVRG4 function resulted in mannosylation defects, which in turn led to a number of cell wall-associated phenotypes. While heterozygotes displayed no growth phenotypes, a hemizygous strain, containing a single copy of CaVRG4 under control of the methionine-repressible MET3 promoter, did not grow in the presence of methionine and cysteine, demonstrating that CaVRG4 is essential for viability. Mutant Candida vrg4 strains were defective in hyphal formation but exhibited a constitutive polarized mode of pseudohyphal growth. Because the VRG4 gene is essential for yeast viability but does not have a mammalian homologue, it is a particularly attractive target for development of antifungal therapies. 相似文献
94.
S Weinstein W Jahn C Glotz F Schlünzen I Levin D Janell J Harms I K?lln H A Hansen M Glühmann W S Bennett H Bartels A Bashan I Agmon M Kessler M Pioletti H Avila K Anagnostopoulos M Peretz T Auerbach F Franceschi A Yonath 《Journal of structural biology》1999,127(2):141-151
Procedures were developed exploiting organometallic clusters and coordination compounds in combination with heavy metal salts for derivatization of ribosomal crystals. These enabled the construction of multiple isomorphous replacement (MIR) and multiple isomorphous replacement combined with anomalous scattering medium-resolution electron density maps for the ribosomal particles that yield the crystals diffracting to the highest resolution, 3 A, of the large subunit from Haloarcula marismortui and the small subunit from Thermus thermophilus. The first steps in the interpretation of the 7. 3-A MIR map of the small subunit were made with the aid of a tetrairidium cluster that was covalently attached to exposed sulfhydryls on the particle's surface prior to crystallization. The positions of these sulfhydryls were localized in difference Fourier maps that were constructed with the MIR phases. 相似文献
95.
Escherichia coli intracellular pH, membrane potential, and cell growth. 总被引:11,自引:13,他引:11
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We studied the changes in various cell functions during the shift to alkaline extracellular pH in wild-type Escherichia coli and in strain DZ3, a mutant defective in pH homeostasis. A rapid increase in membrane potential (delta psi) was detected in both the wild type and the mutant immediately upon the shift, when both cell types failed to control intracellular pH. Upon reestablishment of intracellular pH - extracellular pH and growth in the wild type, delta psi decreased to a new steady-state value. The electrochemical proton gradient (delta muH+) was similar in magnitude to that observed before the pH shift. In the mutant DZ3, delta psi remained elevated, and even though delta muH+ was higher than in the wild type, growth was impaired. Cessation of growth in the mutant is not a result of cell death. Hence, the mutant affords an interesting system to explore the intracellular-pH-sensitive steps that arrest growth without affecting viability. In addition to delta muH+, we measured respiration rates, protein synthesis, cell viability, induction of beta-galactosidase, DNA synthesis, and cell elongation upon failure of pH homeostasis. Cell division was the only function arrested after the shift in extracellular pH. The cells formed long chains with no increase in colony-forming capacity. 相似文献
96.
Heparanase processing by lysosomal/endosomal protein preparation 总被引:6,自引:0,他引:6
Heparanase is an endo-beta-glucuronodase involved in cleavage of heparan sulfate side chains, activity that is strongly implicated in cell dissemination associated with tumor metastasis and inflammation. Heparanase is first synthesized as a latent 65 kDa precursor that is converted into an active enzyme upon proteolytic processing. Previously, we have reported that elevation of the lysosomal pH results in complete inhibition of heparanase processing, suggesting that lysosomal protease(s) and acidic pH conditions are required for heparanase processing. Here, we adopted a cell fractionation approach and provide evidence that incubation of the pro-enzyme with lysosome/endosome, but not with cytoplasmic fractions resulted in processing and activation of the 65 kDa latent heparanase. Moreover, while the water soluble lysosome/endosome fraction exhibited no apparent processing activity, heparanase processing by the water insoluble lysosome/endosome membrane fraction was readily detected and exhibited the expected pH dependency. 相似文献
97.
98.
Mechanisms in the in vivo release of lymphokines. II. Regulation of in vivo release of type II interferon IFN gamma 总被引:2,自引:0,他引:2
R Neta 《Cellular immunology》1981,60(1):100-108
The regulation of IFNγ release was studied in vivo in mice intravenously sensitized with cell walls of BCG (CW/Dr) and challenged with OT. Subcutaneous inoculation with CFA, but not with CW/Dr, following intravenous sensitization, reduced the titers of IFNγ. Similar inoculation prior to intravenous sensitization enhanced the titers of IFNγ in high- and low-responder mice. A substance that suppressed the activity of interferon was detected in the sera of sensitized and challenged low-responder strains. 相似文献
99.
A diffusion Michaelis-Menten mechanism: continuous conformational change in enzymatic kinetics 总被引:1,自引:0,他引:1
N Agmon 《Journal of theoretical biology》1985,113(4):711-717
We present a simple model which extends the Michaelis-Menten mechanism by incorporating a continuous protein conformational change in enzymatic catalysis. This model can represent a quantitative version for "rack" or "induced fit" mechanisms. In the steady-state it leads to an equation of the Michaelis-Menten form, but with the catalytic step at the active site showing strong dependence on solvent viscosity. We suggest that a careful examination of solvent viscosity effects on enzymatic activity may serve as a test for the conformational change hypothesis. 相似文献
100.