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991.
992.
993.
Secretory carrier membrane protein 2 (SCAMP2) functions in late steps of membrane fusion in calcium-dependent granule exocytosis. A basic/hydrophobic peptide segment within SCAMP2 (SCAMP2 E: CWYRPIYKAFR) has been implicated in this function and shown to bind and sequester phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2 or PIP2] within membranes through an electrostatic mechanism. We now show that alanine substitution of tryptophan W2 within SCAMP2 E substantially weakens peptide binding to negatively charged liposomes; other substitutions for arginine R4 and lysine K8 have only limited effects on binding. Electron paramagnetic resonance analysis of liposomes containing spin-labeled PIP2 shows that R4 but not K8 is critical for SCAMP E binding to PIP2. The interfacial locations of SCAMP E and its structural variants within lipid bicelles measured by oxygen enhancement of nuclear relaxation are all similar. Corresponding point mutations within full-length SCAMP2 (SC2-R204A, SC2-K208A, and SC2-W202A) have been analyzed for biological effects on dense core vesicle exocytosis in neuroendocrine PC12 cells. With the same level of overexpression, SC2-R204A but not SC2-K208A inhibited secretion of cotransfected human growth hormone and of noradrenalin. Inhibition by SC2-R204A was the same as or greater than previously observed for SC2-W202A. Analysis of noradrenalin secretion by amperometry showed that inhibitory mutants of SCAMP2 decrease the probability of fusion pore opening and the stability of initially opened but not yet expanded fusion pores. The strong correlation between SCAMP2 E interactions with PIP2 and inhibition of exocytosis, particularly by SC2-R204A, led us to propose that SCAMP2 interaction with PIP2 within the membrane interface regulates fusion pore formation during exocytosis. 相似文献
994.
Yuan C Yang S Liao Z Liang S 《Biochemical and biophysical research communications》2007,352(3):799-804
Three neurotoxins, Jingzhaotoxin-I, -III, and -V (JZTX-I, -III, and -V), isolated from the venom of the Chinese tarantula Chilobrachys Jingzhao, are 29-36-amino acid peptides. Electrophysiological recordings carried out in Xenopus laevis oocytes show that these toxins acted as gating modifier of voltage-dependent K+ channels. They slow the rate of Kv2.1 channel activation and increase the tail current deactivation, suggesting that toxin-bound channels can still open but are modified. JZTX-III selectively inhibits Kv2.1 channels, and JZTX-V exhibits a higher affinity to Kv4.2 channels than to Kv2.1 channels, whereas JZTX-I inhibits Kv2.1 and Kv4.1 channels with low affinity. Structure-function analysis indicates that electrostatic interactions can benefit for toxin affinity and the feature of electrostatic anisotropy may be correlated with the different affinity of the toxins for the Kv2.1 and Kv4.1 channels. Furthermore, phylogenetic analysis of these and other gating modifiers provides clues for the exploration of toxin-channel interaction. 相似文献
995.
996.
The development of fluorescent sensors for organic molecules is of great practical importance in chemical, biological, and pharmaceutical sciences. Using
-tryptophan as an example, we have studied a new way of making polymeric fluorescent sensors using template polymerization or molecular imprinting techniques. The fluorescent polymers were prepared using functional monomers with a fluorescent probe attached to it. The fluorescence of this polymer could be quenched by 4-nitrobenzaldehyde. Addition of the template molecules,
-tryptophan, increased the fluorescence intensity of the imprinted polymer/quencher mixture in a concentration-dependent fashion, presumably through the displacement of the quencher from the binding sites by
-tryptophan. This fluorescence intensity change upon mixing with
-tryptophan allows the binding event to be detected easily. The sensor also exhibited enantioselectivity for the template molecules. For example, the effect of
-tryptophan on the fluorescence intensity of the polymer is about 70% that of its
-enantiomer. Furthermore, the effect of
-phenylalanine and
-alanine on the fluorescence intensity change is much smaller than that of
-tryptophan. Because the approach used does not require the de novo design of the complementary binding site and does not rely on any specific structural features of the template molecule or prior knowledge of its three-dimensional structure, the same principle could potentially be useful for the future construction of practical fluorescent sensors for many other compounds. 相似文献
997.
青海湖裸鲤体腔寄生蠕虫群落研究 总被引:3,自引:2,他引:1
青海湖裸鲤体腔为三种寄生蠕虫寄生,即裂头绦虫裂头蚴,舌状绦虫裂头蚴和对盲囊缄虫的三期幼虫,这几种蠕虫不同大小的青海湖裸鲤中数量差异很大,将其看作一个组分群落,并根据其发生数量进行模糊聚类和极点排序,结果将其分为二个亚组分群落,即体长小于150mm的青海湖裸鲤体腔蠕虫亚组分群落和体长大于150mm的个体的体腔蠕虫亚组分群落。这与宿主的行为和食性改变有密切关系,舌状绦虫与另两种蠕虫间有显著负协调关系。 相似文献
998.
Normal Human Telomeres Are Not Late Replicating 总被引:9,自引:0,他引:9
Woodring E. Wright Valerie M. Tesmer Martha L. Liao Jerry W. Shay 《Experimental cell research》1999,251(2):492-499
Telomeres in yeast are late replicating. Genes placed next to telomeres in yeast can be repressed (telomere positional effects), leading to the hypothesis that telomeres may be heterochromatic and may control the expression of subtelomeric genes. In addition, yeast telomeres are processed to have a transient long overhang at the end of S phase. The applicability of the yeast data to human biology was examined by determining the timing of telomere replication and processing in normal human diploid fibroblasts. Telomeres were purified from synchronized cells that had been labeled with 5-bromodeoxyuridine (BrdU) at hourly intervals, and the fraction of labeled telomeres was analyzed by retrieval with anti-BrdU antibodies. We determined that normal human telomeres replicate throughout S phase rather than being very late replicating. Furthermore, the overall timing of replication was unaffected by telomere length in young versus old cells or cells whose telomeres had been elongated following transfection with the catalytic subunit of telomerase. Finally, the asymmetry in the length of the G-rich overhang in daughter telomeres produced by leading versus lagging strand synthesis was shown to be established within 1 h of telomere replication, indicating there is no significant delay between synthesis and the processing events that contribute to the establishment of asymmetric overhangs. Therefore, the timings of replication and processing of human telomeres are very different from those of yeast. 相似文献
999.
1000.
Ataxia telangiectasia-mutated gene product inhibits DNA damage-induced apoptosis via ceramide synthase. 总被引:5,自引:0,他引:5
W C Liao A Haimovitz-Friedman R S Persaud M McLoughlin D Ehleiter N Zhang M Gatei M Lavin R Kolesnick Z Fuks 《The Journal of biological chemistry》1999,274(25):17908-17917
DNA double-stranded breaks (dsb) activate surveillance systems that identify DNA damage and either initiate repair or signal cell death. Failure of cells to undergo appropriate death in response to DNA damage leads to misrepair, mutations, and neoplastic transformation. Pathways linking DNA dsb to reproductive or apoptotic death are virtually unknown. Here we report that metabolic incorporation of 125I-labeled 5-iodo-2'deoxyuridine, which produces DNA dsb, signaled de novo ceramide synthesis by post-translational activation of ceramide synthase (CS) and apoptosis. CS activation was obligatory, since fumonisin B1, a fungal pathogen that acts as a specific CS inhibitor, abrogated DNA damage-induced death. X-irradiation yielded similar results. Furthermore, inhibition of apoptosis using the peptide caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone did not affect CS activation, indicating this event is not a consequence of induction of apoptosis. ATM, the gene mutated in ataxia telangiectasia, is a member of the phosphatidylinositol 3-kinase family that constitutes the DNA damage surveillance/repair system. Epstein-Barr virus-immortalized B cell lines from six ataxia telangiectasia patients with different mutations exhibited radiation-induced CS activation, ceramide generation, and apoptosis, whereas three lines from normal patients failed to manifest these responses. Stable transfection of wild type ATM cDNA reversed these events, whereas antisense inactivation of ataxia telangiectasia-mutated gene product in normal B cells conferred the ataxia telangiectasia phenotype. We propose that one of the functions of ataxia telangiectasia-mutated gene product is to constrain activation of CS, thereby regulating DNA damage-induced apoptosis. 相似文献