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981.
982.
Wurm S Paar C Sonnleitner A Sonnleitner M Höglinger O Romanin C Wechselberger C 《FEBS letters》2004,566(1-3):121-125
While long-term effects of temperature treatment in respect of, e.g., gene-expression and cellular function have already been studied in some detail, nothing is known on the physiological responses of lymphocytes during short-term hypothermal shifts. In this report, we characterized the effects of such a stimulation using the human lymphocyte cell line Jurkat E6.1 and present evidence that warming from 4 to 37 degrees C for only 2 min is sufficient to cause co-localization of CD3, prion protein and the lipid-raft ganglioside GM1 paralleling lymphocyte activation as observed by Ca(2+) mobilization and mitogen-activated protein kinase-phosphorylation. 相似文献
983.
Brockmann C Leitner D Labudde D Diehl A Sievert V Büssow K Kühne R Oschkinat H 《FEBS letters》2004,558(1-3):101-106
The solution structure of an N-terminally extended construct of the SODD BAG domain was determined by nuclear magnetic resonance spectroscopy. A homology model of the SODD-BAG/HSP70 complex reveals additional possible interactions that are specific for the SODD subfamily of BAG domains while the overall geometry of the complex remains the same. Relaxation rate measurements show that amino acids N358-S375 of SODD which were previously assigned to its BAG domain are not structured in our construct. The SODD BAG domain is thus indeed smaller than the homologous domain in Bag1 defining a new subfamily of BAG domains. 相似文献
984.
Stranzl GR Gruber K Steinkellner G Zangger K Schwab H Kratky C 《The Journal of biological chemistry》2004,279(5):3699-3707
The hydroxynitrile lyase from Hevea brasiliensis (HbHNL) uses a catalytic triad consisting of Ser(80)-His(235)-Asp(207) to enhance the basicity of Ser(80)-O gamma for abstracting a proton from the OH group of the substrate cyanohydrin. Following the observation of a relatively short distance between a carboxyl oxygen of Asp(207) and the N delta(1)(His(235)) in a 1.1 A crystal structure of HbHNL, we here show by (1)H and (15)N-NMR spectroscopy that a short, strong hydrogen bond (SSHB) is formed between the two residues upon binding of the competitive inhibitor thiocyanate to HbHNL: the proton resonance of H-N delta 1(His(235)) moves from 15.41 ppm in the free enzyme to 19.35 ppm in the complex, the largest downfield shift observed so far upon inhibitor binding. Simultaneously, the D/H fractionation factor decreases from 0.98 to 0.35. In the observable pH range, i.e. between pH 4 and 10, no significant changes in chemical shifts (and therefore hydrogen bond strength) were observed for free HbHNL. For the complex with thiocyanate, the 19.35 ppm signal returned to 15.41 ppm at approximately pH 8, which indicates a pK(a) near this value for the H-N epsilon(2)(His(235)). These NMR results were analyzed on the basis of finite difference Poisson-Boltzmann calculations, which yielded the relative free energies of four protonation states of the His(235)-Asp(207) pair in solution as well as in the protein environment with and without bound inhibitor. The calculations explain all the NMR features, i.e. they suggest why a short, strong hydrogen bond is formed upon inhibitor binding and why this short, strong hydrogen bond reverts back to a normal one at approximately pH 8. Importantly, the computations also yield a shift of the free energy of the anionic state relative to the zwitterionic reference state by about 10.6 kcal/mol, equivalent to a shift in the apparent pK(a) of His(235) from 2.5 to 10. This huge inhibitor-induced increase in basicity is a prerequisite for His(235) to act as general base in the HbHNL-catalyzed cyanohydrin reaction. 相似文献
985.
The members of the Bcl-2 family of proteins are crucial regulators of apoptosis. In order to determine cell fate, these proteins must be targeted to distinct intracellular membranes, including the mitochondrial outer membrane (MOM), the membrane of the endoplasmic reticulum (ER) and its associated nuclear envelope. The targeting sequences and mechanisms that mediate the specificity of these proteins for a particular cellular membrane remain poorly defined. Several Bcl-2 family members have been reported to be tail-anchored via their predicted hydrophobic COOH-terminal transmembrane domains (TMDs). Tail-anchoring imposes a posttranslational mechanism of membrane insertion on the already folded protein, suggesting that the transient binding of cytosolic chaperone proteins to the hydrophobic TMD may be an important regulatory event in the targeting process. The TMD of certain family members is initially concealed and only becomes available for targeting and membrane insertion in response to apoptotic stimuli. These proteins either undergo a conformational change, posttranslational modification or a combination of these events enabling them to translocate to sites at which they are functional. Some Bcl-2 family members lack a TMD, but nevertheless localize to the MOM or the ER membrane during apoptosis where they execute their functions. In this review, we will focus on the intracellular targeting of Bcl-2 family members and the mechanisms by which they translocate to their sites of action. Furthermore, we will discuss the posttranslational modifications which regulate these events. 相似文献
986.
Based on recent structural and functional findings, we have constructed a mathematical model for the sodium-driven Fo motor of the F1Fo-ATPase from the anaerobic bacterium Propionigenium modestum. The model reveals the mechanochemical principles underlying the Fo motor's operation, and explains all of the existing experimental data on wild-type and mutant Fo motors. In particular, the model predicts a nonmonotonic dependence of the ATP hydrolysis activity on the sodium concentration, a prediction confirmed by new experiments. To explain experimental observations, the positively charged stator residue (R227) must assume different positions in the ATP synthesis and hydrolysis directions. This work also illustrates how to extract a motor mechanism from dynamical experimental observations in the absence of complete structural information. 相似文献
987.
988.
989.
Litzlbauer HD Neuhaeuser C Moell A Greschus S Breithecker A Franke FE Kummer W Rau WS 《American journal of physiology. Lung cellular and molecular physiology》2006,291(3):L535-L545
We evaluated microfocal X-ray-computed tomography (micro-CT) as a method to visualize lung architecture two and three dimensionally and to obtain morphometric data. Inflated porcine lungs were fixed by formaldehyde ventilation. Tissue samples (8-mm diameter, 10-mm height) were stained with osmium tetroxide, and 400 projection images (1,024 x 1,024 pixel) were obtained. Continuous isometric micro-CT scans (voxel size 9 microm) were acquired to reconstruct two- and three-dimensional images. Tissue samples were sectioned (8-microm thickness) for histological analysis. Alveolar surface density and mean linear intercept were assessed by stereology-based morphometry in micro-CT scans and corresponding histological sections. Furthermore, stereology-based morphometry was compared with morphometric semi-automated micro-CT analysis within the same micro-CT scan. Agreement of methods was assessed by regression and Bland-Altman analysis. Comparing histology with micro-CT, alveolar surface densities (35.4 +/- 2.4 vs. 33.4 +/- 1.9/mm, P < 0.05) showed a correlation (r = 0.72; P = 0.018) with an agreement of 2 +/- 1.6/mm; the mean linear intercept (135.7 +/- 14.5 vs. 135.8 +/- 15 microm) correlated well (r = 0.97; P < 0.0001) with an agreement of -0.1 +/- 3.4 microm. Semi-automated micro-CT analysis resulted in smaller alveolar surface densities (33.4 +/- 1.9 vs. 30.5 +/- 1/mm; P < 0.01) with a correlation (r = 0.70; P = 0.023) and agreement of 2.9 +/- 1.4/mm. Non-destructive micro-CT scanning offers the advantage to visualize the spatial tissue architecture of small lung samples two and three dimensionally. 相似文献
990.