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1.
Species-specific cell adhesion in marine sponges is mediated by a new family of modular proteoglycans whose general supramolecular
structure resembles that of hyalectans. However, neither their protein nor their glycan moieties have significant sequence
homology to other proteoglycans, despite having protein subunits equivalent to link proteins and to proteoglycan monomer core
proteins, and glycan subunits equivalent to hyaluronan and to the glycosaminoglycans of hyalectans. In some species, these
molecular components are assembled into a structure with a circular core formed by the link protein- and hyaluronan-like subunits.
Besides their involvement in cell adhesion, these sponge proteoglycans, for which we propose the term spongicans, participate
in signal transduction processes and are suspected to play a role in sponge self-nonself recognition. Their in vivo roles
and the mild methods used to purify large amounts of functionally active spongicans make them ideal models to study the functions
and possible new applications of proteoglycans in biomedical research.
Received 21 May 2002; received after revision 5 July 2002; accepted 10 July 2002
RID="*"
ID="*"Corresponding author. 相似文献
2.
3.
Effects of myocardial ischemia and reperfusion on mitochondrial function and susceptibility to oxidative stress 总被引:8,自引:0,他引:8
We investigated the effects of ischemia duration on the functional response of mitochondria to reperfusion and its relationship
with changes in mitochondrial susceptibility to oxidative stress. Mitochondria were isolated from hearts perfused by the Langendorff
technique immediately after different periods of global ischemia or reperfusion following such ischemia periods. Rates of
O2 consumption and H2O2 release with complex I- and complex II-linked substrates, lipid peroxidation, overall antioxidant capacity, capacity to remove
H2O2, and susceptibility to oxidative stress were determined. The effects of ischemia on some parameters were time dependent so
that the changes were greater after 45 than after 20 min of ischemia, or were significantly different to the nonischemic control
only after 45 min of ischemia. Thus, succinate-supported state 3 respiration exhibited a significant decrease after 20 min
of ischemia and a greater decrease after 45 min, while pyruvate malate-supported respiration showed a significant decrease
only after 45 min of ischemia, indicating an ischemia-induced early inhibition of complex II and a late inhibition of complex
I. Furthermore, both succinate and pyruvate malate-supported H2O2 release showed significant increases only after 45 min of ischemia. Similarly, whole antioxidant capacity significantly increased
and susceptibility to oxidants significantly decreased after 45 min of ischemia. Such changes were likely due to the accumulation
of reducing equivalents, which are able to remove peroxides and maintain thiols in a reduced state. This condition, which
protects mitochondria against oxidants, increases mitochondrial production of oxyradicals and oxidative damage during reperfusion.
This could explain the smaller functional recovery of the tissue and the further decline of the mitochondrial function after
reperfusion following the longer period of oxygen deprivation.
Received 18 May 2001; received after revision 17 July 2001; accepted 24 July 2001 相似文献
4.
In vitro import studies have confirmed the participation of cytosolic protein factors in the import of various precursor proteins into mitochondria. The requirement for extramitochondrial adenosine triphosphate for the import of a group of precursor proteins seems to be correlated with the chaperone activity of the cytosolic protein factors. One of the cytosolic protein factors is hsp70, which generally recognizes and binds unfolded proteins in the cytoplasm. Hsp70 keeps the newly synthesized mitochondrial precursor proteins in import-competent unfolded conformations. Another cytosolic protein factor that has been characterized is mitochondrial import stimulation factor (MSF), which seems to be specific to mitochondrial precursor proteins. MSF recognizes the mitochondrial precursor proteins, forms a complex with them and targets them to the receptors on the outer surface of mitochondria. 相似文献
5.
sHsps and their role in the chaperone network 总被引:17,自引:0,他引:17
Haslbeck M 《Cellular and molecular life sciences : CMLS》2002,59(10):1649-1657
Small Hsps (sHsps) encompass a widespread but diverse class of proteins. These low molecular mass proteins (15—42 kDa) form
dynamic oligomeric structures ranging from 9 to 50 subunits. sHsps display chaperone function in vitro, and in addition they
have been suggested to be involved in the inhibition of apoptosis, organisation of the cytoskeleton and establishing the refractive
properties of the eye lens in the case of α-crystallin. How these different functions can be explained by a common mechanism
is unclear at present. However, as most of the observed phenomena involve nonnative protein, the repeatedly reported chaperone
properties of sHsps seem to be of key importance for understanding their function. In contrast to other chaperone families,
sHsps bind several nonnative proteins per oligomeric complex, thus representing the most efficient chaperone family in terms
of the quantity of substrate binding. In some cases, the release of substrate proteins from the sHsp complex is achieved in
cooperation with Hsp70 in an ATP-dependent reaction, suggesting that the role of sHsps in the network of chaperones is to
create a reservoir of nonnative refoldable protein. 相似文献
6.
SecB is only one of a plethora of cytosolic chaperones in E. coli whose common property is that they bind nonnative proteins. It plays a crucial role during protein export via the general
secretory pathway by modulating the partitioning of precursors between folding or aggregation and delivery to the membrane-bound
translocation apparatus. In this latter role SecB demonstrates specific binding to a unique partner, SecA. SecB has the potential
to participate in functions outside of export acting as a general nonspecific chaperone to provide buffering capacity of the
nonnative state of proteins in the cytosolic pool. We discuss the interactions of SecB with its many binding partners in light
of its recently determined structure, emphasizing both kinetic and thermodynamic parameters.
RID="*"
ID="*"Corresponding author. 相似文献
7.
The proton-translocating NADH:ubiquinone oxidoreductase or complex I is located in the inner membranes of mitochondria, where
it catalyzes the transfer of electrons from NADH to ubiquinone. Here we report that one of the subunits in complex I is homologous
to short-chain dehydrogenases and reductases, a family of enzymes with diverse activities that include metabolizing steroids,
prostaglandins and nucleotide sugars. We discovered that a subunit of complex I in human, cow, Neurospora crassa and Aquifex aeolius is homologous to nucleotide-sugar epimerases and hydroxysteroid dehydrogenases while seeking distant homologs of these enzymes
with a hidden Markov model-based search of Genpept. This homology allows us to use information from the solved three-dimensional
structures of nucleotide-sugar epimerases and hydroxysteroid dehydrogenases and our motif analysis of these enzymes to predict
functional domains on their homologs in complex I.
Received 26 November 1998; received after revision 12 January 1999; accepted 12 January 1999 相似文献
8.
Heat-shock protein 90, a chaperone for folding and regulation 总被引:21,自引:0,他引:21
Picard D 《Cellular and molecular life sciences : CMLS》2002,59(10):1640-1648
Heat-shock protein 90 (Hsp90) is an abundant and highly conserved molecular chaperone that is essential for viability in
eukaryotes. Hsp90 fulfills a housekeeping function in contributing to the folding, maintenance of structural integrity and
proper regulation of a subset of cytosolic proteins. A remarkable proportion of its substrates are proteins involved in cell
cycle control and signal transduction. Hsp90 acts with a cohort of Hsp90 co-chaperones that modulate its substrate recognition,
ATPase cycle and chaperone function. The large conformational flexibility of Hsp90 and a multitude of dynamic co-chaperone
complexes contribute to generating functional diversity, and allow Hsp90 to assist a wide range of substrates. 相似文献
9.
Davoli C Marconi A Serafino A Iannoni C Marcheggiano A Ravagnan G 《Cellular and molecular life sciences : CMLS》2002,59(3):527-539
Nerve growth factor (NGF) belongs by sequence homology to the neurotrophins, a family of proteins binding the same p75 receptor
and closely related members of the Trk family of receptor tyrosine kinases. Fundamental in the vertebrate nervous system,
neurotrophin signals have also been suggested as essential for relatively complex nervous systems occurring in invertebrate
species that live longer than Caenorhabditis elegans and Drosophila melanogaster. Mammalian neurotrophins have been found to influence invertebrate neuronal growth. However, there are only a few data on
the presence of molecules related to neurotrophin signalling components in invertebrates. Our studies provide evidence that
analogues of neurotrophins and neurotrophin receptors are expressed in Eisenia foetida earthworms. In particular, NGF-like and Trk-like immunoreactive proteins are both expressed in the nervous system, whereas
p75-like positivity identifies tubular structures associated with dorsal pores that are involved in the earthworm response
to mechanical irritation or stress.
Received 12 November 2001; received after revision 8 January 2002; accepted 8 January 2002 相似文献
10.
R.C. May 《Cellular and molecular life sciences : CMLS》2001,58(11):1607-1626
In recent years the Arp2/3 complex has emerged as a central regulator of actin dynamics, assembling and cross-linking actin
filaments to produce a diverse array of cellular structures. Here I discuss our current state of knowledge about this actin-remodelling
machine. The predicted structure of the Arp2/3 complex can be directly correlated with its ability to nucleate, cap and cross-link
actin filaments. A growing family of Arp2/3 complex activators such as the WASP family, type I myosins, and the newly identified
activators cortactin and Abp1p tightly regulate this activity within the cell. Localised activation of the Arp2/3 complex
produces structures such as lamellipodia or actin patches via a process termed dendritic nucleation. Furthermore, several
pathogenic microorganisms have evolved strategies to 'hijack' the Arp2/3 complex to their own advantage. Finally, I discuss
some of the questions which remain unanswered about this fascinating complex.
Received 2 April 2001; received after revision 15 May 2001; accepted 18 May 2001 相似文献
11.
ATP-dependent proteases controlling mitochondrial function in the yeast Saccharomyces cerevisiae 总被引:3,自引:0,他引:3
Regulated protein degradation by ATP-dependent proteases plays a fundamental role in the biogenesis of mitochondria. Membrane-bound and soluble ATP-dependent proteases have been identified in various subcompartments of this organelle. Subunits composing these proteases are evolutionarily conserved from yeast to humans and, in support of an endosymbiotic origin of mitochondria, evolved from prokaryotic ancestors: the PIM1/Lon protease is active in the matrix of mitochondria, while the i-AAA protease and the m-AAA protease mediate the turnover of inner membrane proteins. Most of the knowledge concerning the biogenesis and the physiological role of ATP-dependent proteases comes from studies in the yeast Saccharomyces cerevisiae. Proteases were found to be required for mitochondrial stasis, for the maintenance of the morphology of the organelle and for mitochondrial genome integrity. ATP-dependent proteolysis is crucial for the expression of mitochondrially encoded subunits of respiratory chain complexes and for the assembly of these complexes. Hence, mitochondrial ATP-dependent proteases exert multiple roles which are essential for the maintenance of cellular respiratory competence. 相似文献
12.
13.
Hsp70 chaperones: Cellular functions and molecular mechanism 总被引:36,自引:0,他引:36
Hsp70 proteins are central components of the cellular network of molecular chaperones and folding catalysts. They assist a large variety of protein folding processes in the cell by transient association of their substrate binding domain with short hydrophobic peptide segments within their substrate proteins. The substrate binding and release cycle is driven by the switching of Hsp70 between the low-affinity ATP bound state and the high-affinity ADP bound state. Thus, ATP binding and hydrolysis are essential in vitro and in vivo for the chaperone activity of Hsp70 proteins. This ATPase cycle is controlled by co-chaperones of the family of J-domain proteins, which target Hsp70s to their substrates, and by nucleotide exchange factors, which determine the lifetime of the Hsp70-substrate complex. Additional co-chaperones fine-tune this chaperone cycle. For specific tasks the Hsp70 cycle is coupled to the action of other chaperones, such as Hsp90 and Hsp100.Received 21 October 2004; received after revision 24 November 2004; accepted 6 December 2004 相似文献
14.
Protein farnesylation in mammalian cells: effects of farnesyltransferase inhibitors on cancer cells 总被引:3,自引:0,他引:3
F. Tamanoi C.-L. Gau C. Jiang H. Edamatsu J. Kato-Stankiewicz 《Cellular and molecular life sciences : CMLS》2001,58(11):1636-1649
Protein farnesylation, catalyzed by protein farnesyltransferase, plays important roles in the membrane association and protein-protein
interaction of a number of eukaryotic proteins. Recent development of farnesyltransferase inhibitors (FTIs) has led to further
insight into the biological significance of farnesylation in cancer cells. A number of reports point to the dramatic effects
FTIs exert on cancer cells. In addition to inhibiting anchorage-independent growth, FTIs cause changes in the cell cycle either
at the G1/S or at the G2/M phase. Furthermore, induction of apoptosis by FTIs has been reported. FTIs also affects the actin
cytoskeleton and cell morphology. This review summarizes these reports and discusses implications for farnesylated proteins
responsible for these FTI effects.
Received 17 April 2001; received after revision 28 May 2001; accepted 28 May 2001 相似文献
15.
Human mitochondrial tRNAs in health and disease 总被引:6,自引:0,他引:6
Florentz C Sohm B Tryoen-Tóth P Pütz J Sissler M 《Cellular and molecular life sciences : CMLS》2003,60(7):1356-1375
The human mitochondrial genome encodes 13 proteins, all subunits of the respiratory chain
complexes and thus involved in energy metabolism. These genes are translated by 22 transfer RNAs
(tRNAs), also encoded by the mitochondrial genome, which form the minimal set required for reading
all codons. Human mitochondrial tRNAs gained interest with the rapid discovery of correlations
between point mutations in their genes and various neuromuscular and neurodegenerative disorders.
In this review, emerging fundamental knowledge on the structure/function relationships of these
particular tRNAs and an overview of the large variety of mechanisms within translation, affected by
mutations, are summarized. Also, initial results on wide-ranging molecular consequences of mutations
outside the frame of mitochondrial translation are highlighted. While knowledge of mitochondrial
tRNAs in both health and disease increases, deciphering the intricate network of events leading
different genotypes to the variety of phenotypes requires further investigation using adapted
model systems.Received 3 December 2002; received after revision 14 January 2003; accepted 27 January 2003 相似文献
16.
Trimeric guanine nucleotide-binding proteins (G proteins) function as the key regulatory elements in a number of transmembrane
signaling cascades where they convey information from agonist-activated receptors to effector molecules. The subcellular localization
of G proteins is directly related to their functional role, i.e., the dominant portion of the cellular pool of G proteins
resides in the plasma membrane. An intimate association of G protein subunits with the plasma membrane has been well known
for a long time. However, results of a number of independent studies published in the past decade have indicated clearly that
exposure of intact target cells to agonists results in subcellular redistribution of the cognate G proteins from plasma membranes
to the light-vesicular membrane fractions, in internalization from the cell surface into the cell interior and in transfer
from the membrane to the soluble cell fraction (high-speed supernatant), i.e., solubilization. Solubilization of G protein
α subunits as a consequence of stimulation of G protein-coupled receptors (GPCRs) with agonists has also been observed in
isolated membrane preparations. The membrane-cytosol shift of G proteins was detected even after direct activation of these
proteins by non-hydrolyzable analogues of GTP or by cholera toxin-induced ADP-ribosylation. In addition, prolonged stimulation
of GPCRs with agonists has been shown to lead to down-regulation of the relevant G proteins. Together, these data suggest
that G proteins might potentially participate in a highly complex set of events, which are generally termed desensitization
of the hormone response. Internalization, subcellular redistribution, solubilization, and down-regulation of trimeric G proteins
may thus provide an additional means (i.e., beside receptor-based mechanisms) to dampen the hormone or neurotransmitter response
after sustained (long-term) exposure.
Received 31 August 2001; received after revision 31 October 2001; accepted 7 November 2001 相似文献
17.
Identification of tyrosine-phosphorylated proteins of the mitochondrial oxidative phosphorylation machinery 总被引:1,自引:1,他引:0
Augereau O Claverol S Boudes N Basurko MJ Bonneu M Rossignol R Mazat JP Letellier T Dachary-Prigent J 《Cellular and molecular life sciences : CMLS》2005,62(13):1478-1488
The role of some serine/threonine kinases in the regulation of mitochondrial physiology is now well established, but little is known about mitochondrial tyrosine kinases. We showed that tyrosine phosphorylation of rat brain mitochondrial proteins was increased by in vitro addition of ATP and H2O2, and also during in situ ATP production at state 3, and maximal reactive oxygen species production. The Src kinase inhibitor PP2 decreased tyrosine phosphorylation and respiratory rates at state 3. We found that the 39-kDa subunit of complex I was tyrosine phosphorylated, and we identified putative tyrosine-phosphorylated subunits for the other complexes. We also have strong evidence that the FoF1-ATP synthase α chain is probably tyrosine-phosphorylated, but demonstrated that the β chain is not. The tyrosine phosphatase PTP 1B was found in brain but not in muscle, heart or liver mitochondria. Our results suggest that tyrosine kinases and phosphatases are involved in the regulation of oxidative phosphorylation.Received 7 January 2005; received after revision 19 April 2005; accepted 22 April 2005 相似文献
18.
Microtubules are fibrous elements in the cytoplasm of eukaryotic cells, where they perform a wide variety of functions. Microtubules
are major organizers of the cell interior and are vitally involved in motility events such as chromosome migration during
cell division. To fulfill their physiological function, microtubule arrays have to undergo dramatic changes in their spatial
arrangement, and this depends to a large extent on the complex and special dynamic properties of the individual polymers.
In this review we first describe the intrinsic dynamic properties of microtubules assembled in vitro from purified tubulin
and examine the relationships between these properties and microtubule functions. Subsequent sections concern microtubule
dynamics in vivo, their similarity and differences with microtubule dynamics in vitro, and the nature of the cellular regulators
which act on microtubule assemblies in physiological conditions.
Received 2 May 2001; received after revision 10 July 2001; accepted 10 July 2001 相似文献
19.
The cdk-activating kinase (CAK): from yeast to mammals 总被引:25,自引:0,他引:25
Kaldis P 《Cellular and molecular life sciences : CMLS》1999,55(2):284-296
20.
de Keyzer J van der Does C Driessen AJ 《Cellular and molecular life sciences : CMLS》2003,60(10):2034-2052
The major route of protein translocation in bacteria is the so-called general secretion pathway (Sec-pathway). This route has been extensively studied in Escherichia coli and other bacteria. The movement of preproteins across the cytoplasmic membrane is mediated by a multimeric membrane protein complex called translocase. The core of the translocase consists of a proteinaceous channel formed by an oligomeric assembly of the heterotrimeric membrane protein complex SecYEG and the peripheral adenosine triphosphatase (ATPase) SecA as molecular motor. Many secretory proteins utilize the molecular chaperone SecB for targeting and stabilization of the unfolded state prior to translocation, while most nascent inner membrane proteins are targeted to the translocase by the signal recognition particle and its membrane receptor. Translocation is driven by ATP hydrolysis and the proton motive force. In the last decade, genetic and biochemical studies have provided detailed insights into the mechanism of preprotein translocation. Recent crystallographic studies on SecA, SecB and the SecYEG complex now provide knowledge about the structural features of the translocation process. Here, we will discuss the mechanistic and structural basis of the translocation of proteins across and the integration of membrane proteins into the cytoplasmic membrane.Received 10 January 2003; received after revision 2 April 2003; accepted 4 April 2003 相似文献