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排序方式: 共有185条查询结果,搜索用时 15 毫秒
41.
42.
Plant gene expression in response to pathogens 总被引:13,自引:0,他引:13
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Lewis PA Properzi F Prodromidou K Clarke AR Collinge J Jackson GS 《The Biochemical journal》2006,395(2):443-448
According to the protein-only hypothesis of prion propagation, prions are composed principally of PrP(Sc), an abnormal conformational isoform of the prion protein, which, like its normal cellular precursor (PrP(C)), has a GPI (glycosylphosphatidylinositol) anchor at the C-terminus. To date, elucidating the role of this anchor on the infectivity of prion preparations has not been possible because of the resistance of PrP(Sc) to the activity of PI-PLC (phosphoinositide-specific phospholipase C), an enzyme which removes the GPI moiety from PrP(C). Removal of the GPI anchor from PrP(Sc) requires denaturation before treatment with PI-PLC, a process that also abolishes infectivity. To circumvent this problem, we have removed the GPI anchor from PrP(Sc) in RML (Rocky Mountain Laboratory)-prion-infected murine brain homogenate using the aspartic endoprotease cathepsin D. This enzyme eliminates a short sequence at the C-terminal end of PrP to which the GPI anchor is attached. We found that this modification has no effect (i) on an in vitro amplification model of PrP(Sc), (ii) on the prion titre as determined by a highly sensitive N2a-cell based bioassay, or (iii) in a mouse bioassay. These results show that the GPI anchor has little or no role in either the propagation of PrP(Sc) or on prion infectivity. 相似文献
45.
Wells MA Jelinska C Hosszu LL Craven CJ Clarke AR Collinge J Waltho JP Jackson GS 《The Biochemical journal》2006,400(3):501-510
Although the physiological function of the prion protein remains unknown, in vitro experiments suggest that the protein may bind copper (II) ions and play a role in copper transport or homoeostasis in vivo. The unstructured N-terminal region of the prion protein has been shown to bind up to six copper (II) ions, with each of these ions co-ordinated by a single histidine imidazole and nearby backbone amide nitrogen atoms. Individually, these sites have micromolar affinities, which is weaker than would be expected of a true cuproprotein. In the present study, we show that with subsaturating levels of copper, different forms of co-ordination will occur, which have higher affinity. We have investigated the copper-binding properties of two peptides representing the known copper-binding regions of the prion protein: residues 57-91, which contains four tandem repeats of the octapeptide GGGWGQPH, and residues 91-115. Using equilibrium dialysis and spectroscopic methods, we unambiguously demonstrate that the mode of copper co-ordination in both of these peptides depends on the number of copper ions bound and that, at low copper occupancy, copper ions are co-ordinated with sub-micromolar affinity by multiple histidine imidazole groups. At pH 7.4, three different modes of copper co-ordination are accessible within the octapeptide repeats and two within the peptide comprising residues 91-115. The highest affinity copper (II)-binding modes cause self-association of both peptides, suggesting a role for copper (II) in controlling prion protein self-association in vivo. 相似文献
46.
Shadoo (Sprn) and prion disease incubation time in mice 总被引:1,自引:0,他引:1
Prion diseases are transmissible neurodegenerative disorders of mammalian species and include scrapie, bovine spongiform encephalopathy
(BSE), and variant Creutzfeldt-Jakob disease (vCJD). The prion protein (PrP) plays a key role in the disease, with coding
polymorphism in both human and mouse influencing disease susceptibility and incubation time, respectively. Other genes are
also thought to be important and a plausible candidate is Sprn, which encodes the PrP-like protein Shadoo (Sho). Sho is expressed in the adult central nervous system and exhibits neuroprotective
activity reminiscent of PrP in an in vitro assay. To investigate the role of Sprn in prion disease incubation time we sequenced the open reading frame (ORF) in a diverse panel of mice and saw little variation
except in strains derived from wild-trapped mice. Sequencing the untranslated regions revealed polymorphisms that allowed
us to carry out an association study of incubation period in the Northport heterogeneous stock of mice inoculated with Chandler/RML
prions. We also examined the expression level of Sprn mRNA in the brains of normal and prion-infected mice and saw no correlation with either genotype or incubation time. We therefore
conclude that Sprn does not play a major role in prion disease incubation time in these strains of mice. 相似文献
47.
Disease-related prion protein, PrP(Sc), is classically distinguished from its normal cellular precursor, PrP(C), by its detergent insolubility and partial resistance to proteolysis. Molecular diagnosis of prion disease typically relies upon detection of protease-resistant fragments of PrP(Sc) using proteinase K, however it is now apparent that the majority of disease-related PrP and indeed prion infectivity may be destroyed by this treatment. Here we report that digestion of RML prion-infected mouse brain with pronase E, followed by precipitation with sodium phosphotungstic acid, eliminates the large majority of brain proteins, including PrP(C), while preserving >70% of infectious prion titre. This procedure now allows characterization of proteinase K-sensitive prions and investigation of their clinical relevance in human and animal prion disease without being confounded by contaminating PrP(C). 相似文献
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Altitudinal changes in traits and genetic markers can complement the studies on latitudinal patterns and provide evidence of natural selection because of climatic factors. In Drosophila melanogaster, latitudinal variation is well known but altitudinal patterns have rarely been investigated. Here, we examine five traits and five genetic markers on chromosome 3R in D. melanogaster collected at high and low altitudes from five latitudes along the eastern coast of Australia. Significant altitudinal differentiation was observed for cold tolerance, development time, ovariole number in unmated females, and the microsatellite marker DMU25686. Differences tended to match latitudinal patterns, in that trait values at high altitudes were also found at high latitudes, suggesting that factors linked to temperature are likely selective agents. Cold tolerance was closely associated with average temperature and other climatic factors, but no significant associations were detected for the other traits. Genes around DMU25686 represent good candidates for climatic adaptation. 相似文献
50.
In animals infected with a transmissible spongiform encephalopathy, or prion disease, conformational isomers (known as PrPSc proteins) of the wild-type, host-encoded cellular prion protein (PrPc) accumulate. The infectious agents, prions, are composed mainly of these conformational isomers, with distinct prion isolates or strains being associated with different PrPSc conformations and patterns of glycosylation. Here we show that two different human PrPSc types, seen in clinically distinct subtypes of classical Creutzfeldt-Jakob disease, can be interconverted in vitro by altering their metal-ion occupancy. The dependence of PrPSc conformation on the binding of copper and zinc represents a new mechanism for post-translational modification of PrP and for the generation of multiple prion strains, with widespread implications for both the molecular classification and the pathogenesis of prion diseases in humans and animals. 相似文献