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71.
72.
Curtain CC Ali F Volitakis I Cherny RA Norton RS Beyreuther K Barrow CJ Masters CL Bush AI Barnham KJ 《The Journal of biological chemistry》2001,276(23):20466-20473
Amyloid beta peptide (Abeta) is the major constituent of extracellular plaques and perivascular amyloid deposits, the pathognomonic neuropathological lesions of Alzheimer's disease. Cu(2+) and Zn(2+) bind Abeta, inducing aggregation and giving rise to reactive oxygen species. These reactions may play a deleterious role in the disease state, because high concentrations of iron, copper, and zinc have been located in amyloid in diseased brains. Here we show that coordination of metal ions to Abeta is the same in both aqueous solution and lipid environments, with His(6), His(13), and His(14) all involved. At Cu(2+)/peptide molar ratios >0.3, Abeta coordinated a second Cu(2+) atom in a highly cooperative manner. This effect was abolished if the histidine residues were methylated at N(epsilon)2, indicating the presence of bridging histidine residues, as found in the active site of superoxide dismutase. Addition of Cu(2+) or Zn(2+) to Abeta in a negatively charged lipid environment caused a conformational change from beta-sheet to alpha-helix, accompanied by peptide oligomerization and membrane penetration. These results suggest that metal binding to Abeta generated an allosterically ordered membrane-penetrating oligomer linked by superoxide dismutase-like bridging histidine residues. 相似文献
73.
Zn(2+) modulation of neuronal transient K(+) current: fast and selective binding to the deactivated channels 总被引:1,自引:0,他引:1 下载免费PDF全文
Modulation of voltage-dependent transient K(+) currents (A type K(+) or K(A) current) by Zn(2+) was studied in rat hippocampal neurons by the whole-cell patch-clamp technique. It is found that Zn(2+) selectively binds to the resting (deactivated or closed) K(A) channels with a dissociation constant (K(d)) of approximately 3 &mgr;M, whereas the affinity between Zn(2+) and the inactivated K(A) channels is 1000-fold lower. Zn(2+) therefore produces a concentration-dependent shift of the K(A) channel inactivation curve and enhances the K(A) current elicited from relatively positive holding potentials. It is also found that the kinetics of Zn(2+) action are fast enough to compete with the transition rates between different gating states of the channel. The rapid and selective binding of Zn(2+) to the closed K(A) channels keeps the channel in the closed state and explains the ion's concentration-dependent slowing effect on the activation of K(A) current. This in turn accounts for the inhibitory effect of Zn(2+) on the K(A) current elicited from hyperpolarized holding potentials. Because the molecular mechanisms underlying these gating changes are kinetic interactions between the binding-unbinding of Zn(2+) and the intrinsic gating processes of the channel, the shift of the inactivation curve and slowing of K(A) channel activation are quantitatively correlated with ambient Zn(2+) over a wide concentration range without "saturation"; i.e., The effects are already manifest in micromolar Zn(2+), yet are not saturated even in millimolar Zn(2+). Because the physiological concentration of Zn(2+) could vary over a similarly wide range according to neural activities, Zn(2+) may be a faithful physiological "fine tuner," controlling and controlled by neural activities through its effect on the K(A) current. 相似文献
74.
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1972. Parasite antigens and host antibodies in Ostertagia circumcincta infection of the sheep. International Journal for Parasitology, 2: 449–457. An allergenic component was separated from Ostertagia circumcincta antigens and specific reaginic antibody was separated from the corresponding 7S antibodies in sheep sera. Further evidence was obtained that the immunoglobulin class defined as IgG1A contains the reaginic or homocytotropic antibodies in sheep. Both the IgG1A antibody and P.C.A. levels continued to increase after the expulsion of the parasites, whereas the levels of anti-Ostertagia IgG1 did not. 相似文献
76.
Changes in the ordering of lipids in the membrane of Dunaliella in response to osmotic-pressure changes. An e.s.r. study. 总被引:2,自引:0,他引:2 下载免费PDF全文
Changes in the ordering and motion of lipids in response to changes in the external solute concentration have been studied by using the 5-nitroxide stearate (5NS) and 16-nitroxide stearate (16NS) spin probes in the plasma membrane of the halotolerant unicellular alga Dunaliella salina. Increases in ordering of the 5NS probe and decreases in motion of the 16NS probe were observed in cells equilibrated over 18 h at increasing NaCl concentrations. These changes probably resulted from the influence of the high NaCl concentration on the charged phospholipid head groups of the membrane. A short-term (less than 100 min) decrease in the order parameter, S, of the 5NS probe was observed for cells swollen by exposure to a sudden decrease of NaCl concentration from 5.0 to 2.5 M. After 100 min the value of S for 5NS was close to the value obtained in cells that had been equilibrated in 2.5 M-NaCl for 18 h. Since the cells had regained their original size and shape by 100 min it was assumed that the short-term decrease in S was associated with the swelling. A similar result was obtained when the cells were suddenly changed from 3.0 M- to 1.5 M-sorbitol. Conversely, an increase in S was observed for cells shrunk when the external solute concentration was doubled from 1.5 M- to 3.0 M-NaCl. As the cells regained their original size and shape the value of S decreased to the value observed in cells that had been equilibrated in 3.0 M-NaCl for 18 h. It is suggested that the changes in S are related to the movement of lipid into or out of a reservoir of membrane material as the membrane shrinks or expands. This movement of lipid maintains the tension of the membrane below the value at which it is disrupted. Such changes in lipid ordering could provide a mechanism whereby information about external osmotic-pressure changes is transmitted across the cell wall. 相似文献
77.
The distribution of the Gc phenotypes was determined by immunoelectrophoresis amongst 486 inhabitants of nine villages of the Markham River Valley of New Guinea. The overall gene frequencies were Gc1, 0.538; Gc2, 0.351; GcAborigine, 0.112. GcAborigine occurred in all the villages, its frequency ranging from 0.041 to 0.187. The Gc2 gene frequency also varied widely ranging from 0.167 to 0.491. No correlation could be found between altitude and the Gc distribution and there was an overlap in the gene frequencies between the Austronesian and non-Austronesian-speaking villages. 相似文献
78.
BD Pascal MJ Chalmers SA Busby CC Mader MR Southern NF Tsinoremas PR Griffin 《BMC bioinformatics》2007,8(1):156
Background
The combination of mass spectrometry and solution phase amide hydrogen/deuterium exchange (H/D exchange) experiments is an effective method for characterizing protein dynamics, and protein-protein or protein-ligand interactions. Despite methodological advancements and improvements in instrumentation and automation, data analysis and display remains a tedious process. The factors that contribute to this bottleneck are the large number of data points produced in a typical experiment, each requiring manual curation and validation, and then calculation of the level of backbone amide exchange. Tools have become available that address some of these issues, but lack sufficient integration, functionality, and accessibility required to address the needs of the H/D exchange community. To date there is no software for the analysis of H/D exchange data that comprehensively addresses these issues. 相似文献79.
80.
CC van Diemen DS Postma M Siedlinski A Blokstra HA Smit HM Boezen 《Respiratory research》2011,12(1):57