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1.
Summary. The accumulation of oxidized proteins is known to be linked to some severe neurodegenerative diseases like Alzheimer’s, Parkinson’s
and Huntington’s disease. Furthermore, the aging process is also accompanied by an ongoing aggregation of misfolded and damaged
proteins. Therefore, mammalian cells have developed potent degradation systems, which selectively degrade damaged and misfolded
proteins. The proteasomal system is largely responsible for the removal of oxidatively damaged proteins form the cellular
environment. Not only cytosolic proteins are prone to oxidative stress, also nuclear proteins are readily oxidized. The nuclear
proteasomal system is responsible for the degradation of these proteins. This review is focused on the specific degradation
of oxidized nuclear proteins, the role of the proteasome in this process and the regulation of the nuclear proteasomal system
under oxidative conditions. 相似文献
2.
Most proteins involved in plastid biogenesis are encoded by the nuclear genome. They are synthesised in the cytosol and have
to be transported toward and subsequently translocated into the organelle. This targeting and import process is initiated
by a specific chloroplast-targeting signal. The targeting signal of the preprotein is recognised and modified by cytosolic
proteins which function in transport toward the chloroplast and in maintaining the import-competent state of the preprotein.
The precursor is transferred onto a multi-component complex in the outer envelope of the chloroplasts, which is formed by
receptor proteins and the translocation channel. Some proteins, not containing transit sequences, are directly sorted into
the outer membrane whereas the majority, containing transit sequences, will be translocated into the stroma. This involves
the joint action of a protein complex in the outer envelope, one complex in the inner envelope, and soluble proteins in the
intermembrane space and the stroma. The origin of this translocation complex following the endosymbiotic events is an unsolved
question. Recent identification of homologous proteins to some members of this machinery in the cyanobacterium Synechocystis PCC6803 gives an initial insight into the origin of the translocation complex.
Received: 27 December 1999 / Accepted: 29 March 2000 相似文献
3.
Catabolism of native and oxidized low density lipoproteins: in vivo insights from small animal positron emission tomography studies 总被引:5,自引:0,他引:5
Summary. The human organism is exposed to numerous processes that generate reactive oxygen species (ROS). ROS may directly or indirectly
cause oxidative modification and damage of proteins. Protein oxidation is regarded as a crucial event in the pathogenesis
of various diseases ranging from rheumatoid arthritis to Alzheimer’s disease and atherosclerosis. As a representative example,
oxidation of low density lipoprotein (LDL) is regarded as a crucial event in atherogenesis. Data concerning the role of circulating
oxidized LDL (oxLDL) in the development and outcome of diseases are scarce. One reason for this is the shortage of methods
for direct assessment of the metabolic fate of circulating oxLDL in vivo. We present an improved methodology based on the radiolabelling of apoB-100 of native LDL (nLDL) and oxLDL, respectively,
with the positron emitter fluorine-18 (18F) by conjugation with N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB). Radiolabelling of both nLDL and oxLDL using [18F]SFB causes neither additional oxidative structural modifications of LDL lipids and proteins nor alteration of their biological
activity and functionality, respectively, in vitro. The method was further evaluated with respect to the radiopharmacological properties of both [18F]fluorobenzoylated nLDL and oxLDL by biodistribution studies in male Wistar rats. The metabolic fate of [18F]fluorobenzoylated nLDL and oxLDL in rats in vivo was further delineated by dynamic positron emission tomography (PET) using a dedicated small animal tomograph (spatial resolution
of 2 mm). From this study we conclude that the use of [18F]FB-labelled LDL particles is an attractive alternative to, e.g., LDL iodination methods, and is of value to characterize
and to discriminate the kinetics and the metabolic fate of nLDL and oxLDL in small animals in vivo. 相似文献
4.
Barre A Peumans WJ Menu-Bouaouiche L Van Damme EJ May GD Herrera AF Van Leuven F Rougé P 《Planta》2000,211(6):791-799
The pulp of ripe bananas (Musa acuminata) contains an abundant thaumatin-like protein (TLP). Characterization of the protein and molecular cloning of the corresponding
gene from banana demonstrated that the native protein consists of a single polypeptide chain of 200 amino acid residues. Molecular
modelling further revealed that the banana thaumatin-like protein (Ban-TLP) adopts an overall fold similar to that of thaumatin
and thaumatin-like PR-5 proteins. Although the banana protein exhibits an electrostatically polarized surface, which is believed
to be essential for the antifungal properties of TLPs, it is apparently devoid of antifungal activity towards pathogenic fungi.
It exhibits a low but detectable in vitro endo-β-1,3-glucanase (EC 3.2.1.x) activity. As well as being present in fruits,
Ban-TLP also occurs in root tips where its accumulation is enhanced by methyl jasmonate treatment of plants. Pulp of plantains
(Musa acuminata) also contains a very similar TLP, which is even more abundant than its banana homologue. Our results demonstrate for the
first time that fruit-specific (abundant) TLPs are not confined to dicots but occur also in fruits of monocot species. The
possible role of the apparent widespread accumulation of fruit-specific TLPs is discussed.
Received: 7 January 2000 / Accepted: 26 April 2000 相似文献
5.
This paper describes efforts of the structural genomics project in the nuclear magnetic resonance (NMR) laboratory at the
University of Science and Technology of China. This structural genomics project is biological-functional driven. Targets are
mainly selected from two systems: proteins related with regulation of gene expression in humans and other eukaryotes, and
proteins existing in the cell junction in humans. The majority of proteins selected from these two systems are related with
human health and diseases, and some are potential drug targets. Twenty-five protein structures from Homo sapiens and other
eukaryotes have been determined during last 5 years in this laboratory. Nuclear magnetic resonance (NMR) spectroscopy is highly
suited to investigate molecular interactions at a close physiological condition and is particularly suited for the study of
low-affinity, transient complexes. It can provide information on protein surface interaction, their complex structure, and
their dynamic properties during protein recognition. Several examples are given in this paper. 相似文献
6.
7.
Myelin Proteomics: Molecular Anatomy of an Insulating Sheath 总被引:1,自引:0,他引:1
Fast-transmitting vertebrate axons are electrically insulated with multiple layers of nonconductive plasma membrane of glial
cell origin, termed myelin. The myelin membrane is dominated by lipids, and its protein composition has historically been
viewed to be of very low complexity. In this review, we discuss an updated reference compendium of 342 proteins associated
with central nervous system myelin that represents a valuable resource for analyzing myelin biogenesis and white matter homeostasis.
Cataloging the myelin proteome has been made possible by technical advances in the separation and mass spectrometric detection
of proteins, also referred to as proteomics. This led to the identification of a large number of novel myelin-associated proteins,
many of which represent low abundant components involved in catalytic activities, the cytoskeleton, vesicular trafficking,
or cell adhesion. By mass spectrometry-based quantification, proteolipid protein and myelin basic protein constitute 17% and
8% of total myelin protein, respectively, suggesting that their abundance was previously overestimated. As the biochemical
profile of myelin-associated proteins is highly reproducible, differential proteome analyses can be applied to material isolated
from patients or animal models of myelin-related diseases such as multiple sclerosis and leukodystrophies. 相似文献
8.
Empirical evidence shows that childhood diseases persist in large communities whereas in smaller communities the epidemic
goes extinct (and is later reintroduced by immigration). The present paper treats a stochastic model describing the spread
of an infectious disease giving life-long immunity, in a community where individuals die and new individuals are born. The
time to extinction of the disease starting in quasi-stationarity (conditional on non-extinction) is exponentially distributed.
As the population size grows the epidemic process converges to a diffusion process. Properties of the limiting diffusion are
used to obtain an approximate expression for τ, the mean-parameter in the exponential distribution of the time to extinction
for the finite population. The expression is used to study how τ depends on the community size but also on certain properties
of the disease/community: the basic reproduction number and the means and variances of the latency period, infectious period
and life-length. Effects of introducing a vaccination program are also discussed as is the notion of the critical community
size, defined as the size which distinguishes between the two qualitatively different behaviours.
Received: 14 February 2000 / Revised version: 5 June 2000 / Published online: 24 November 2000 相似文献
9.
Summary. Phosphate transport in bacteria occurs via a phosphate specific transporter system (PSTS) that belongs to the ABC family of
transporters, a multisubunit system, containing an alkaline phosphatase. DING proteins were characterized due to the N-terminal
amino acid sequence DINGG GATL, which is highly conserved in animal and plant isolates, but more variable in microbes. Most
prokaryotic homologues of the DING proteins often have some structural homology to phosphatases or periplasmic phosphate-binding
proteins. In E. coli, the product of the inducible gene DinG, possesses ATP hydrolyzing helicase enzymic activity. An alkaline phosphorolytic enzyme of the PSTS system was purified
to homogeneity from the thermophilic bacterium Thermus thermophilus. N-terminal sequence analysis of this protein revealed the same high degree of similarity to DING proteins especially to
the human synovial stimulatory protein P205, the steroidogenesis-inducing protein and to the phosphate ABC transporter, periplasmic
phosphate-binding protein, putative (P. fluorescens Pf-5). The enzyme had a molecular mass of 40 kDa on SDS/PAGE, exhibiting optimal phosphatase activity at pH 12.3 and 70 °C.
The enzyme possessed characteristics of a DING protein, such as ATPase, ds endonuclease and 3′ phosphodiesterase (3′-exonuclease)
activities and binding to linear dsDNA, displaying helicase activity on supercoiled DNA. Purification and biochemical characterization
of a T. thermophilus DING protein was achieved. The biochemical properties, N-terminal sequence similarities of this protein implied that the
enzyme belongs to the PSTS family and might be involved in the DNA repair mechanism of this microorganism.
Authors’ address: Assist. Prof. A. A. Pantazaki, Laboratory of Biochemistry, Department of Chemistry, Aristotle University
of Thessaloniki, Thessaloniki 54124, Greece 相似文献
10.
Summary. The pathogenesis of several neurodegenerative diseases, including Alzheimer’s disease, has been linked to a condition of oxidative
and nitrosative stress, arising from the imbalance between increased reactive oxygen species (ROS) and reactive nitrogen species
(RNS) production and antioxidant defences or efficiency of repair or removal systems. The effects of free radicals are expressed
by the accumulation of oxidative damage to biomolecules: nucleic acids, lipids and proteins. In this review we focused our
attention on the large body of evidence of oxidative damage to protein in Alzheimer’s disease brain and peripheral cells as
well as in their role in signalling pathways. The progress in the understanding of the molecular alterations underlying Alzheimer’s
disease will be useful in developing successful preventive and therapeutic strategies, since available drugs can only temporarily
stabilize the disease, but are not able to block the neurodegenerative process. 相似文献
11.
Summary. Thermophilic proteins show substantially higher intrinsic thermal stability than their mesophilic counterparts. Amino acid
composition is believed to alter the intrinsic stability of proteins. Several investigations and mutagenesis experiment have
been carried out to understand the amino acid composition for the thermostability of proteins. This review presents some generalized
features of amino acid composition found in thermophilic proteins, including an increase in residue hydrophobicity, a decrease
in uncharged polar residues, an increase in charged residues, an increase in aromatic residues, certain amino acid coupling
patterns and amino acid preferences for thermophilic proteins. The differences of amino acids composition between thermophilic
and mesophilic proteins are related to some properties of amino acids. These features provide guidelines for engineering mesophilic
protein to thermophilic protein.
Authors’ addresses: Yuan-Jiang Pan, Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Zhejiang
University Road 38, Hangzhou 310027, China; Wei-Fen Li, Microbiology Division, College of Animal Science, Zhejiang University,
Hangzhou 310029, China 相似文献
12.
Summary. To date, the majority of therapeutic peptides and proteins have to be administered via parenteral routes, which are painful
and inconvenient. In order to gain sufficient high blood concentrations after oral application, various barriers in the gastrointestinal
tract have to be overcome. Apart from a poor membrane uptake and intense enzymatic degradation, this study will demonstrate
that thiol–disulphide reactions are an underestimated essential part of the presystemic metabolism. Glutathione, integrative
part of the antioxidant defence system in the gastrointestinal tract, may play an important role in the inactivation of orally
given peptides and proteins. In order to verify this hypothesis, desmopressin which bears a single disulphide bond was used
as model peptide drug. Desmopressin was incubated with GSH in various concentrations, and the extent of thiol/disulphide exchange
reactions between the peptide drug and GSH was investigated in dependence on pH and ratio of reactants determined as a function
of time via HPLC, LC-MS and Maldi-Tof-MS analyses.
Results showed that desmopressin is degraded by 1% reduced glutathione at pH 4 and pH 5.5. In presence of 0.01%, 0.1% and
1% of reduced glutathione 6.1%, 19.4% and 52.1% of desmopressin, respectively, were degraded. The masses of the conjugates
after deconvolution measured by liquid chromatography and electrospray ionisation mass spectrometric detection were m/z 1069.67, m/z 1376.50, m/z 1683.40 and m/z 2138. These molecular masses, confirmed by Maldi-Tof-MS analysis, correspond with the masses of conjugates expected in theory.
Under defined conditions, these results reveal that thiol–disulphide exchange reactions have a considerable impact on the
alteration of peptide drugs and proteins. 相似文献
13.
《Molecular membrane biology》2013,30(2):67-78
SummaryThe segregation of proteins to specific cellular membranes is recognized as a common phenomenon. In oligodendrocytes of the central nervous system, localization of certain proteins to select regions of the plasma membrane gives rise to the myelin membrane. Whilst the fundamental structure and composition of myelin is well understood, less is known of the mechanisms by which the constituent proteins are specifically recruited to those regions of plasma membrane that are forming myelin. The two principal proteins of myelin, the myelin basic protein and proteolipid protein, differ greatly in character and sites of synthesis. The message for myelin basic protein is selectively translocated to the ends of the cell processes, where it is translated on free ribosomes and is incorporated directly into the membrane. Proteolipid protein synthesized at the rough endoplasmic reticulum, processed through the Golgi apparatus, and presumably transported via vesicles to the myelin membrane. This review examines the mechanisms by which these two proteins are targeted to the myelin membrane. 相似文献
14.
Summary. Amino acids are widely used in biotechnology applications. Since amino acids are natural compounds, they can be safely used
in pharmaceutical applications, e.g., as a solvent additive for protein purification and as an excipient for protein formulations.
At high concentrations, certain amino acids are found to raise intra-cellular osmotic pressure and adjust to the high salt
concentrations of the surrounding medium. They are called “compatible solutes”, since they do not affect macromolecular function.
Not only are they needed to increase the osmotic pressure, they are known to increase the stability of the proteins. Sucrose,
glycerol and certain amino acids were used to enhance the stability of unstable proteins after isolation from natural environments.
The mechanism of the action of these protein-stabilizing amino acids is relatively well understood. On the contrary, arginine
was accidentally discovered as a useful reagent for assisting in the refolding of recombinant proteins. This effect of arginine
was ascribed to its ability to suppress aggregation of the proteins during refolding, thereby increasing refolding efficiency.
By the same mechanism, arginine now finds much wider applications than previously anticipated in the research and development
of proteins, in particular in pharmaceutical applications. For example, arginine solubilizes proteins from loose inclusion
bodies, resulting in efficient production of active proteins. Arginine suppresses protein–protein interactions in solution
and also non-specific adsorption to gel permeation chromatography columns. Arginine facilitates elution of bound proteins
from various column resins, including Protein-A or dye affinity columns and hydrophobic interaction columns. This review covers
various biotechnology applications of amino acids, in particular arginine. 相似文献
15.
The silk of caterpillars is secreted in the labial glands, stored as a gel in their lumen, and converted into a solid filament
during spinning. Heavy chain fibroin (H-fibroin), light chain fibroin (L-fibroin), and P25 protein constitute the filament
core in a few species that have been analyzed. Identification of these proteins in Yponomeuta evonymella, a moth from a family which diverged from the rest of Lepidoptera about 150 million years ago, reveals that the mode of filament
construction is highly conserved. It is proposed that association of the three proteins is suited for long storage of hydrated
silk dope and its rapid conversion to filament. Interactions underlying these processes depend on conserved spacing of critical
amino acid residues that are dispersed through the L-fibroin and P25 and assembled in the short ends of the H-fibroin molecule.
Strength, elasticity, and other physical properties of the filament are determined by simple amino acid motifs arranged in
repetitive modules that build up most of the H-fibroin. H-Fibroin synergy with L-fibroin and P25 does not interfere with motif
diversification by which the filament acquires new properties. Several types of motifs in complex repeats occur in the silks
used for larval cobwebs and pupal cocoons. Restriction of silk use to cocoon construction in some lepidopteran families has
been accompanied by simplification of H-fibroin repeats. An extreme deviation of the silk structure occurs in the Saturniidae
silkmoths, which possess modified H-fibroin and lack L-fibroin and P25.
[Reviewing Editor: Dr. David Pollok] 相似文献
16.
Summary. Transmembrane (TM) proteins represent about 20–30% of the protein sequences in higher eukaryotes, playing important roles
across a range of cellular functions. Moreover, knowledge about topology of these proteins often provides crucial hints toward
their function. Due to the difficulties in experimental structure determinations of TM protein, theoretical prediction methods
are highly preferred in identifying the topology of newly found ones according to their primary sequences, useful in both
basic research and drug discovery. In this paper, based on the concept of pseudo amino acid composition (PseAA) that can incorporate
sequence-order information of a protein sequence so as to remarkably enhance the power of discrete models (Chou, K. C., Proteins:
Structure, Function, and Genetics, 2001, 43: 246–255), cellular automata and Lempel-Ziv complexity are introduced to predict
the TM regions of integral membrane proteins including both α-helical and β-barrel membrane proteins, validated by jackknife
test. The result thus obtained is quite promising, which indicates that the current approach might be a quite potential high
throughput tool in the post-genomic era. The source code and dataset are available for academic users at liml@scu.edu.cn.
Authors’ address: Menglong Li, College of Chemistry, Sichuan University, Chengdu, Sichuan 610064, P.R. China 相似文献
17.
Amino acid analysis by hydrophilic interaction chromatography coupled on-line to electrospray ionization mass spectrometry 总被引:1,自引:0,他引:1
Summary. Collagens form a common family of triple-helical proteins classified in 21 types. This unique structure is further stabilized
by specific hydroxylation of distinct lysyl and prolyl residues forming 5-hydroxylysine and hydroxyproline (Hyp) isomers,
mostly 4-trans and 3-trans-Hyp. The molecular distribution of the Hyp-isomers among the different collagen types is still
not well investigated, even though disturbances in the hydroxylation of collagens are likely to be involved in several diseases
such as osteoporosis and autoimmune diseases. Here, a new approach to analyze underivatized amino acids by hydrophilic interaction
chromatography (HILIC) coupled on-line to electrospray ionization mass spectrometry (ESI-MS) is reported. This method can
separate all three studied Hyp-isomers, Ile, and Leu, which are all isobaric, allowing a direct qualitative and quantitative
analysis of collagen hydrolysates. The sensitivity and specificity was increased by a neutral loss scan based on the loss
of formic acid (46 u). 相似文献
18.
Wood formation in poplar: identification, characterization, and seasonal variation of xylem proteins 总被引:9,自引:0,他引:9
Proteins that are preferentially produced in developing xylem may play a substantial role in xylogenesis. To reveal the identity
of these proteins, comparative two-dimensional polyacrylamide gel electrophoresis was performed on young differentiating xylem,
mature xylem, and bark of poplar (Populus trichocarpa Hook. cv. `Trichobel') harvested at different times of the year. The most-abundant xylem proteins were identified by microsequence
analysis. For 17 of these proteins a putative function could be assigned based on similarity with previously characterized
proteins, and for 15 out of these corresponding expressed sequence tags (ESTs) were found in the poplar EST database. The
identified xylem–preferential proteins, defined by comparing the protein patterns from xylem and bark, were all involved in
the phenylpropanoid pathway: two caffeoyl-coenzyme A O-methyltransferases (CCoAOMT), one phenylcoumaran benzylic ether reductase (PCBER), one bispecific caffeic acid/5-hydroxyferulic
acid O-methyltransferase (COMT), five S-adenosyl-L-methionine synthetases, and one homologue of glycine hydroxymethyltransferase (GHMT). Remarkably, the biological function
of the two most-abundant xylem-preferential proteins (PCBER and a GHMT homologue) remains unclear. In addition, several housekeeping
enzymes were identified: two enolases, two glutamine synthetases, one 70-kDa heat-shock cognate, one calreticulin, and one
α-tubulin. In comparison to the xylem-preferential proteins, the housekeeping proteins were expressed at significant levels
in the bark as well. Also, several additional protein spots were detected for CCoAOMT, PCBER, and COMT by immunoblot. Our
data show that for the study of xylogenesis, two-dimensional protein gel comparisons combined with systematic protein sequencing
may yield information complementary to that from EST sequencing strategies.
Received: 28 June 1999 / Accepted: 3 September 1999 相似文献
19.
Hydrophobic Regions in Myelin Proteins Characterized Through Analysis of "Hydropathic"Profiles 总被引:2,自引:2,他引:0
Michael J. Weise 《Journal of neurochemistry》1985,44(1):163-170
Computer-generated "hydropathic" profiles were constructed for graphic comparison of the amino acid sequences for P2 protein, 18.5 kilodalton (kDa) myelin basic protein (BP), and myelin proteolipid protein (PLP). Profiles were also obtained for cytochrome b5, a membrane protein known to be capable of reversible association with lipid bilayers and of a size comparable to that of the myelin BPs. Analysis of the PLP sequence produced profiles generally compatible with the suggestions that PLP has three transbilayer and two bilayer intercalating segments. Profiles for P2 and 18.5 kDa BP were found to contain hydrophilic segments separated by relatively short hydrophobic regions. Whereas hydropathic indices in hydrophobic regions of P2, 18.5 kDa BP, and PLP fall in the value ranges recently reported for cores of globular proteins and intrabilayer domains of membrane proteins, hydrophobic sections of P2 and 18.5 kDa BP have hydropathic indices similar to those in the hydrophobic core (transprotein) regions of globular proteins. None of them are comparable to the region of cytochrome b5 known to anchor that protein in its membrane or to the segments of PLP sequence proposed as intrabilayer domains. This comparison suggests that neither BP has structural characteristics compatible with insertion into the hydrocarbon core of the myelin lipid bilayer, a conclusion that is consistent with a recently published study that identified the bilayer penetrating proteins of myelin with a hydrophobic probe. The above findings suggest an enhancement for some details of myelin architecture and a cautious approach to interpreting data for BP intercalation into bilayers. 相似文献
20.
The flagella of the green alga Scherffelia dubia are covered by scales which consist of acidic polysaccharides and glycoproteins. Experimental deflagellation results in the
regeneration of flagella complete with scales. During flagellar regeneration, scales are newly synthesized in the Golgi apparatus,
exocytosed and deposited on the growing flagella. Flagellar regeneration is dependent upon protein synthesis and N-glycosylation,
as it is blocked by cycloheximide and partially inhibited by tunicamycin. Metabolic labeling with [35S]methionine/cysteine demonstrated that scale-associated proteins were not newly synthesized during flagellar regeneration,
suggesting that the proteins deposited on regenerating flagella were drawn from a pool. Quantitative immunoelectron microscopy
using a monospecific antibody directed against a scale-associated protein of 126 kDa (SAP126) revealed that the pool of SAP126
was primarily located at the plasma membrane, with minor labeling of the scale reticulum and trans-Golgi cisternae, both before deflagellation and during flagellar regeneration. Since SAP126 was sequestered during flagellar
regeneration into secretory vesicles together with newly synthesized scales, it is concluded that the persistent presence
of SAP126 in the trans-Golgi cisternae during scale biogenesis requires retrograde transport of the protein from the plasma membrane to the Golgi
apparatus.
Received: 3 July 1999 / Accepted: 21 August 1999 相似文献