共查询到20条相似文献，搜索用时 31 毫秒
1.
2.
A variety of quality control mechanisms operate in the endoplasmic reticulum and in downstream compartments of the secretory pathway to ensure the fidelity and regulation of protein expression during cell life and differentiation. As a rule, only proteins that pass a stringent selection process are transported to their target organelles and compartments. If proper maturation fails, the aberrant products are degraded. Quality control improves folding efficiency by retaining proteins in the special folding environment of the endoplasmic reticulum, and it prevents harmful effects that could be caused by the deployment of incompletely folded or assembled proteins. 相似文献
3.
The endoplasmic reticulum (ER) supports disulfide bond formation by a poorly understood mechanism requiring protein disulfide isomerase (PDI) and ERO1. In yeast, Ero1p-mediated oxidative folding was shown to depend on cellular flavin adenine dinucleotide (FAD) levels but not on ubiquinone or heme, and Ero1p was shown to be a FAD-binding protein. We reconstituted efficient oxidative folding in vitro using FAD, PDI, and Ero1p. Disulfide formation proceeded by direct delivery of oxidizing equivalents from Ero1p to folding substrates via PDI. This kinetic shuttling of oxidizing equivalents could allow the ER to support rapid disulfide formation while maintaining the ability to reduce and rearrange incorrect disulfide bonds. 相似文献
4.
葡萄糖调节蛋白78(Glucose regulated protein 78ku, GRP78)又称免疫球蛋白重链结合蛋白(Immunoglobulin heavy chain binding protein, Bip),是位于内质网上的一种重要分子伴侣,属热休克蛋白70家族的一员,GRP78分子及其DNA分子序列结构在许多生物物种中高度保守.GRP78在内质网中参与阻止内质网新生肽聚集、调节内质网钙稳态、抗内质网相关性细胞凋亡以及启动未折叠蛋白反应等.近年来发现,GRP78与多种疾病发生发展密切相关,GRP78生物学功能研究已经引起广泛关注. 相似文献
5.
Electron microscopy of rat hepatocytes revealed a diurnal variation in the relative amounts of endoplasmic reticulum structures and regional differences in their distribution within the hepatic lobule. The diurnal changes in smooth and rough endoplasmic reticulum structures were compared with the diurnal changes in the hepatic microsomal enzyme hexobarbital oxidase. In the control group, at the time when enzyme activity was maximum, the amount of smooth endoplasmic reticulum was also maximum and vice versa. When the enzyme rhythm was abolished, as in blinded rats, the diurnal rhythm in the endoplasmic reticulum was also abolished. 相似文献
6.
概述了蛋白质品质管理中涉及的分子伴侣、激发未折叠蛋白反应(unfolded protein response, UPR)和内质网相关性蛋白质降解途径(ER-associated degradation, ERAD)等的研究进展,并探讨了该领域存在的问题以及发展前景。指出蛋白质的生命过程经历生成、折叠、组装和降解,每个过程都有严格控制。内质网中,各种蛋白质合成、折叠并经修饰形成具有一定构象的功能性蛋白。其在内质网折叠受阻碍时,未折叠的蛋白聚集,激发 UPR,使一系列分子伴侣和蛋白质折叠所需修饰酶类表达上调,帮助其完成折叠和装配。如果这些蛋白仍不能正确折叠,则进入 ERAD 被降解。 相似文献
7.
A variety of molecular chaperones and folding enzymes assist the folding of newly synthesized proteins in the endoplasmic reticulum. Here we investigated why some glycoproteins interact with the molecular chaperone BiP, and others with the calnexin/calreticulin pathway. The folding of Semliki forest virus glycoproteins and influenza hemagglutinin was studied in living cells. The initial choice of chaperone depended on the location of N-linked glycans in the growing nascent chain. Direct interaction with calnexin and calreticulin without prior interaction with BiP occurred if glycans were present within about 50 residues of the protein's NH2-terminus. 相似文献
8.
概述了蛋白质品质管理中涉及的分子伴侣、激发未折叠蛋白反应(unfolded protein response,UPR)和内质网相关性蛋白质降解途径(ER-associated degradation,ERAD)等的研究进展,并探讨了该领域存在的问题以及发展前景。指出蛋白质的生命过程经历生成、折叠、组装和降解,每个过程都有严格控制。内质网中,各种蛋白质合成、折叠并经修饰形成具有一定构象的功能性蛋白。其在内质网折叠受阻碍时,未折叠的蛋白聚集,激发UPR,使一系列分子伴侣和蛋白质折叠所需修饰酶类表达上调,帮助其完成折叠和装配。如果这些蛋白仍不能正确折叠,则进入ERAD被降解。 相似文献
9.
10.
Mediation of the attachment or fusion step in vesicular transport by the GTP-binding Ypt1 protein 总被引：32，自引：0，他引：32
N Segev 《Science (New York, N.Y.)》1991,252(5012):1553-1556
The function of the guanosine triphosphate (GTP)-binding protein Ypt1 in regulating vesicular traffic was studied in a cell-free system that reconstitutes transport from the endoplasmic reticulum to the Golgi. Blocking the Ypt1 protein activity resulted in accumulation of vesicles that act as an intermediate passing between the two compartments. The Ypt1 protein was found on the outer side of these vesicles. The transport process is completed by fusion of these vesicles with the acceptor compartment, and Ypt1 protein activity was needed for this step. Thus, a specific GTP-binding protein is required for either attachment or fusion (or both) of secretory vesicles with the acceptor compartment during protein secretion. 相似文献
11.
Viperin is an interferon-inducible protein that is directly induced in cells by human cytomegalovirus (HCMV) infection. Why HCMV would induce viperin, which has antiviral activity, is unknown. We show that HCMV-induced viperin disrupts cellular metabolism to enhance the infectious process. Viperin interaction with the viral protein vMIA resulted in viperin relocalization from the endoplasmic reticulum to the mitochondria. There, viperin interacted with the mitochondrial trifunctional protein that mediates β-oxidation of fatty acids to generate adenosine triphosphate (ATP). This interaction with viperin, but not with a mutant lacking the viperin iron-sulfur cluster-binding motif, reduced cellular ATP generation, which resulted in actin cytoskeleton disruption and enhancement of infection. This function of viperin, which was previously attributed to vMIA, suggests that HCMV has coopted viperin to facilitate the infectious process. 相似文献
12.
Changes in prion protein (PrP) folding are associated with fatal neurodegenerative disorders, but the neurotoxic species is unknown. Like other proteins that traffic through the endoplasmic reticulum, misfolded PrP is retrograde transported to the cytosol for degradation by proteasomes. Accumulation of even small amounts of cytosolic PrP was strongly neurotoxic in cultured cells and transgenic mice. Mice developed normally but acquired severe ataxia, with cerebellar degeneration and gliosis. This establishes a mechanism for converting wild-type PrP to a highly neurotoxic species that is distinct from the self-propagating PrP(Sc) isoform and suggests a potential common framework for seemingly diverse PrP neurodegenerative disorders. 相似文献
13.
Peptide binding and release by proteins implicated as catalysts of protein assembly 总被引：107，自引：0，他引：107
Two members of the hsp70 family, termed hsc70 and BiP, have been implicated in promoting protein folding and assembly processes in the cytoplasm and the lumen of the endoplasmic reticulum, respectively. Short hydrophilic (8 to 25 residues) synthetic peptides have now been tested as possible mimics of polypeptide chain substrates to help define an enzymatic basis for these activities. Both BiP and hsc70 have specific peptide binding sites. Peptide binding elicits hydrolysis of adenosine triphosphate, with the subsequent release of bound peptide. 相似文献
14.
The vast majority of proteins that a cell secretes or displays on its surface first enter the endoplasmic reticulum (ER), where they fold and assemble. Only properly assembled proteins advance from the ER to the cell surface. To ascertain fidelity in protein folding, cells regulate the protein-folding capacity in the ER according to need. The ER responds to the burden of unfolded proteins in its lumen (ER stress) by activating intracellular signal transduction pathways, collectively termed the unfolded protein response (UPR). Together, at least three mechanistically distinct branches of the UPR regulate the expression of numerous genes that maintain homeostasis in the ER or induce apoptosis if ER stress remains unmitigated. Recent advances shed light on mechanistic complexities and on the role of the UPR in numerous diseases. 相似文献
15.
Expression of bovine 17 alpha-hydroxylase cytochrome P-450 cDNA in nonsteroidogenic (COS 1) cells 总被引：12，自引：0，他引：12
Cortisol production requires the activity of only 17 alpha-hydroxylase, whereas the formation of sex steroids requires both 17 alpha-hydroxylase and 17,20-lyase activities. Studies in reconstituted enzyme systems have suggested that a single steroid hydroxylase, 17 alpha-hydroxylase cytochrome P-450 (P-450(17) alpha), catalyzes both activities. By expression of bovine adrenocortical P-450(17 alpha) in COS 1 (transformed monkey kidney) cells, which normally contain no detectable P-450(17) alpha, it has now been established in situ that a single polypeptide chain does catalyze both the 17 alpha-hydroxylase and the 17,20-lyase reactions. This heterologous system supports 17 alpha-hydroxylation of pregnenolone and progesterone with equal efficiency, but catalyzes about five times as much 17,20-lyase activity when 17 alpha-hydroxypregnenolone is the substrate than when 17 alpha-hydroxyprogesterone is the substrate. For these activities to be observed in COS 1 cells, newly synthesized apocytochrome P-450(17) alpha must bind heme and insert into the endoplasmic reticulum such that endogenous cytochrome P-450 reductase can support hydroxylation. Thus, COS 1 cells are a useful system for expression and study of various forms of cytochrome P-450. 相似文献
16.
Unfolded proteins in the endoplasmic reticulum cause trans-autophosphorylation of the bifunctional transmembrane kinase Ire1, which induces its endoribonuclease activity. The endoribonuclease initiates nonconventional splicing of HAC1 messenger RNA to trigger the unfolded-protein response (UPR). We explored the role of Ire1's kinase domain by sensitizing it through site-directed mutagenesis to the ATP-competitive inhibitor 1NM-PP1. Paradoxically, rather than being inhibited by 1NM-PP1, drug-sensitized Ire1 mutants required 1NM-PP1 as a cofactor for activation. In the presence of 1NM-PP1, drug-sensitized Ire1 bypassed mutations that inactivate its kinase activity and induced a full UPR. Thus, rather than through phosphorylation per se, a conformational change in the kinase domain triggered by occupancy of the active site with a ligand leads to activation of all known downstream functions. 相似文献
17.
宿主因子TRAM1(translocation-associated membrane protein 1,TRAM1)是一种参与I型膜蛋白质分解的蛋白,通过升高含量来缓解内质网(ER)在应激时的压力。前期研究发现,鸭呼肠孤病毒(duck reovirus,DRV)感染原代鸭成纤维细胞后,TRAM1宿主因子变化异常。为确定宿主细胞TRAM1因子与DRV非结构蛋白σNS是否存在相互作用以及相互作用对DRV复制的影响,本实验首先表达σNS蛋白,通过GST融合蛋白沉降技术(GST pull-down)发现TRAM1蛋白与σNS蛋白在细胞外存在相互作用;通过免疫共沉淀(co-immunoprecipitation, Co-IP)试验证实二者在细胞内存在相互作用。过表达TRAM1能够从转录水平抑制DRV σNS的表达,而抑制TRAM1提高σNS的转录水平。本研究为进一步分析σNS蛋白在DRV复制过程中的功能以及为σNS蛋白与宿主因子TRAM1互作对DRV复制的影响提供试验依据。 相似文献
18.
PRRSV GP5基因含有一段信号肽及3个跨膜功能区,这些区域可以使翻译的GP5停留在内质网,从而抑制其表达.根据实验室分离测定的PRRSV T1株GP5基因序列进行优化设计,通过人工合成获得GP5-ShortDNA并构建表达载体pGEX-GP5,将其转入大肠杆菌BL21,经IPTG诱导表达获得约41kD的目的融合蛋白.通过Western-blot检测,结果显示该融合蛋白可与PRRSV阳性血清发生特异性反应,表明该蛋白具有免疫学活性.研究结果为PRRSV基因工程苗的研究奠定了基础,同时也为基因的优化提供了借鉴. 相似文献
19.
Rabbit antiserums were prepared against three submicrosomal fractions from liver of normal or phenobarbital-treated rats. The two membrane fractions originating from the rough- and smooth-surfaced endoplasmic reticulum were characterized by the same soluble antigens, with the exception of a highly basic coinponent present only in extracts of rough membranes. The third fraction, whose subcellular origin is unknown, was different. It contained at least two typical marker antigens not present in the other fractions. Of eight tissue antigens common for the endoplasmic reticulum, five displayed nonspecific esterase activity. Some of these esterases were also found in other organs, but none was seen in rat serum. Phenobarbital treatment of the rats led to a rise in activity and characteristic changes in the esterase patterns of all these submicrosomal liver fractions. 相似文献
20.
Some nascent proteins that fold within the endoplasmic reticulum (ER) never reach their native state. Misfolded proteins are removed from the folding machinery, dislocated from the ER into the cytosol, and degraded in a series of pathways collectively referred to as ER-associated degradation (ERAD). Distinct ERAD pathways centered on different E3 ubiquitin ligases survey the range of potential substrates. We now know many of the components of the ERAD machinery and pathways used to detect substrates and target them for degradation. Much less is known about the features used to identify terminally misfolded conformations and the broader role of these pathways in regulating protein half-lives. 相似文献