排序方式: 共有45条查询结果,搜索用时 361 毫秒
31.
Wyatt AR Yerbury JJ Berghofer P Greguric I Katsifis A Dobson CM Wilson MR 《Cellular and molecular life sciences : CMLS》2011,68(23):3919-3931
The extracellular deposition of misfolded proteins is a characteristic of many debilitating age-related disorders. However,
little is known about the specific mechanisms that act to suppress this process in vivo. Clusterin (CLU) is an extracellular
chaperone that forms stable and soluble complexes with misfolded client proteins. Here we explore the fate of complexes formed
between CLU and misfolded proteins both in vitro and in a living organism. We show that proteins injected into rats are cleared
more rapidly from circulation when complexed with CLU as a result of their more efficient localization to the liver and that
this clearance is delayed by pre-injection with the scavenger receptor inhibitor fucoidan. The CLU–client complexes were found
to bind preferentially, in a fucoidan-inhibitable manner, to human peripheral blood monocytes and isolated rat hepatocytes
and in the latter cell type were internalized and targeted to lysosomes for degradation. The data suggest, therefore, that
CLU plays a key role in an extracellular proteostasis system that recognizes, keeps soluble, and then rapidly mediates the
disposal of misfolded proteins. 相似文献
32.
Christina M. Dobson Samuel J. Hempel Stephanie H. Stalnaker Ryan Stuart Lance Wells 《Cellular and molecular life sciences : CMLS》2013,70(16):2849-2857
Glycosylation of proteins is arguably the most prevalent co- and post-translational modification. It is responsible for increased heterogeneity and functional diversity of proteins. Here we discuss the importance of one type of glycosylation, specifically O-mannosylation and its relationship to a number of human diseases. The most widely studied O-mannose modified protein is alpha-dystroglycan (α-DG). Recent studies have focused intensely on α-DG due to the severity of diseases associated with its improper glycosylation. O-mannosylation of α-DG is involved in cancer metastasis, arenavirus entry, and multiple forms of congenital muscular dystrophy [1, 2]. In this review, we discuss the structural and functional characteristics of O-mannose-initiated glycan structures on α-DG, enzymes involved in the O-mannosylation pathway, and the diseases that are a direct result of disruptions within this pathway. 相似文献
33.
A retrovirus-like strategy for expression of a fusion protein encoded by yeast transposon Ty1 总被引:48,自引:0,他引:48
Eukaryotic transposons such as the Ty element of yeast or the copia-like sequences of Drosophila show structural and functional similarities to both prokaryotic transposons and retroviral proviruses, but the prokaryotic transposons and retroviral proviruses use markedly different expression strategies which yield products having entirely different functions. To determine the phylogenetic relationship between eukaryotic transposons, prokaryotic transposons and retroviruses, we have sought to identify and characterize the proteins encoded by the yeast Ty element and to describe the strategies used to express these proteins. We show here that the yeast transposon produces a fusion protein by a specific frameshifting event that fuses two out-of-phase open reading frames (ORFs). The process is remarkably similar to that used by retroviruses such as Rous sarcoma virus (RSV) to produce Pr180gag-pol. 相似文献
34.
Multiple conformations of a protein demonstrated by magnetization transfer NMR spectroscopy 总被引:11,自引:0,他引:11
It is generally accepted that a globular protein in its native state adopts a single, well-defined conformation. However, there have been several reports that some proteins may exist in more than one distinct folded form in equilibrium. In the case of staphylococcal nuclease, evidence for multiple conformations has come from electrophoretic and NMR studies, although there has been some controversy as to whether these are actually interconvertible forms of the same molecular species. Recently, magnetization transfer (MT)-NMR has been developed as a means of studying the kinetics of conformational transitions in proteins. In the study reported here, this approach has been extended and used to demonstrate the presence of at least two native forms of nuclease in equilibrium and to study their interconversion with the unfolded state under the conditions of the thermal unfolding transition. The experiments reveal that two distinct native forms of the protein fold and unfold independently and that these can interconvert directly as well as via the unfolded state. The spectra of the different forms suggest that they are structurally similar but the MT experiments show that the kinetics of folding and unfolding are quite different. Characterization of this behaviour will, therefore, have important implications for our understanding of the relationship between structure and folding kinetics. 相似文献
35.
Introduced species and their missing parasites 总被引:53,自引:0,他引:53
Damage caused by introduced species results from the high population densities and large body sizes that they attain in their new location. Escape from the effects of natural enemies is a frequent explanation given for the success of introduced species. Because some parasites can reduce host density and decrease body size, an invader that leaves parasites behind and encounters few new parasites can experience a demographic release and become a pest. To test whether introduced species are less parasitized, we have compared the parasites of exotic species in their native and introduced ranges, using 26 host species of molluscs, crustaceans, fishes, birds, mammals, amphibians and reptiles. Here we report that the number of parasite species found in native populations is twice that found in exotic populations. In addition, introduced populations are less heavily parasitized (in terms of percentage infected) than are native populations. Reduced parasitization of introduced species has several causes, including reduced probability of the introduction of parasites with exotic species (or early extinction after host establishment), absence of other required hosts in the new location, and the host-specific limitations of native parasites adapting to new hosts. 相似文献
36.
In order for any biological system to function effectively, it is essential to avoid the inherent tendency of proteins to aggregate and form potentially harmful deposits. In each of the various pathological conditions associated with protein deposition, such as Alzheimer's and Parkinson's diseases, a specific peptide or protein that is normally soluble is deposited as insoluble aggregates generally referred to as amyloid. It is clear that the aggregation process is generally initiated from partially or completely unfolded forms of the peptides and proteins associated with each disease. Here we show that the intrinsic effects of specific mutations on the rates of aggregation of unfolded polypeptide chains can be correlated to a remarkable extent with changes in simple physicochemical properties such as hydrophobicity, secondary structure propensity and charge. This approach allows the pathogenic effects of mutations associated with known familial forms of protein deposition diseases to be rationalized, and more generally enables prediction of the effects of mutations on the aggregation propensity of any polypeptide chain. 相似文献
37.
Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases 总被引:68,自引:0,他引:68
Bucciantini M Giannoni E Chiti F Baroni F Formigli L Zurdo J Taddei N Ramponi G Dobson CM Stefani M 《Nature》2002,416(6880):507-511
A range of human degenerative conditions, including Alzheimer's disease, light-chain amyloidosis and the spongiform encephalopathies, is associated with the deposition in tissue of proteinaceous aggregates known as amyloid fibrils or plaques. It has been shown previously that fibrillar aggregates that are closely similar to those associated with clinical amyloidoses can be formed in vitro from proteins not connected with these diseases, including the SH3 domain from bovine phosphatidyl-inositol-3'-kinase and the amino-terminal domain of the Escherichia coli HypF protein. Here we show that species formed early in the aggregation of these non-disease-associated proteins can be inherently highly cytotoxic. This finding provides added evidence that avoidance of protein aggregation is crucial for the preservation of biological function and suggests common features in the origins of this family of protein deposition diseases. 相似文献
38.
39.
Determining how a protein folds is a central problem in structural biology. The rate of folding of many proteins is determined by the transition state, so that a knowledge of its structure is essential for understanding the protein folding reaction. Here we use mutation measurements--which determine the role of individual residues in stabilizing the transition state--as restraints in a Monte Carlo sampling procedure to determine the ensemble of structures that make up the transition state. We apply this approach to the experimental data for the 98-residue protein acylphosphatase, and obtain a transition-state ensemble with the native-state topology and an average root-mean-square deviation of 6 A from the native structure. Although about 20 residues with small positional fluctuations form the structural core of this transition state, the native-like contact network of only three of these residues is sufficient to determine the overall fold of the protein. This result reveals how a nucleation mechanism involving a small number of key residues can lead to folding of a polypeptide chain to its unique native-state structure. 相似文献
40.
A. -K. Borg-Karlson L. Ågren H. Dobson G. Bergström 《Cellular and molecular life sciences : CMLS》1988,44(6):531-534
Summary Both geranyl hexanoate and geranyl octanoate were identified by GC/MS as the major volatiles in a hitherto uncharacterized abdominal gland in females inAgriotes obscurus. Only geranyl octanoate was found inA. lineatus. In EAG tests performed onA. obscurus males, geranyl butanoate and geranyl hexanoate elicited the strongest antennal responses.Financial assistance was donated by The Bank of Sweden Tercentenary Foundation and the Axel and Margaret Ax: son Johnson Foundation. We thank B Baur for statistical advice. 相似文献