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1.
Infection of bacteria triggers innate immune defense reactions in Drosophila. So far, the only bacterial component known to be recognized by the insect innate immune system is peptidoglycan, one of
the most abundant constituents of the bacterial cell wall. Insects use peptidoglycan recognition proteins to detect peptidoglycan
and to activate innate immune responses. Such specialized peptidoglycan receptors appear to have evolved from phage enzymes
that hydrolyze bacterial cell walls. They are able to bind specific peptidoglycan molecules with distinct chemical moieties
and activate innate immune pathways by interacting with other signaling proteins. Recent X-ray crystallographic studies of
the peptidoglycan recognition proteins LCa, and LCx bound to peptidoglycan have provided structural insights into recognition
of peptidoglycan and activation of innate immunity in insects.
Received 28 December 2006; received after revision 2 February 2007; accepted 21 February 2007 相似文献
2.
Recognition of bacterial peptidoglycan by the innate immune system 总被引:15,自引:0,他引:15
Dziarski R 《Cellular and molecular life sciences : CMLS》2003,60(9):1793-1804
The innate immune system recognizes microorganisms through a series of pattern recognition receptors that are highly conserved in evolution. Peptidoglycan (PGN) is a unique and essential component of the cell wall of virtually all bacteria and is not present in eukaryotes, and thus is an excellent target for the innate immune system. Indeed, higher eukaryotes, including mammals, have several PGN recognition molecules, including CD14, Toll-like receptor 2, a family of peptidoglycan recognition proteins, Nod1 and Nod2, and PGN-lytic enzymes (lysozyme and amidases). These molecules induce host responses to microorganisms or have direct antimicrobial effects.Received 15 January 2003; received after revision 28 February 2003; accepted 26 March 2003 相似文献
3.
Jedrzejas MJ 《Cellular and molecular life sciences : CMLS》2007,64(21):2799-2822
Bacteria present a variety of molecules either on their surface or in a cell-free form. These molecules take part in numerous
processes in the interactions with their host, with its tissues and other molecules. These molecules are essential to bacterial
pathogenesis either during colonization or the spread/invasion stages, and most are virulence factors. This review is focused
on such molecules using Streptococcus pneumoniae, a Gram-positive bacterium, as an example. Selected surface proteins are introduced, their structure described, and, whenever
available, their mechanisms of function on an atomic level are explained. Such mechanisms for hyaluronate lyase, pneumococcal
surface protein A, pneumolysin, histidine-triad and fibronectin-binding proteins are discussed. Elucidation of molecular mechanisms
of virulence factors is essential for the understanding of bacteria and their functional properties. Structural biology appears
pivotal for these studies, as structural and mechanistic insights facilitate rational approach to the development of new treatments.
Received 12 March 2007; received after revision 28 June 2007; accepted 18 July 2007 相似文献
4.
Dependence receptors: between life and death 总被引:2,自引:0,他引:2
The recently described family of dependence receptors is a new family of functionally related receptors.
These proteins have little sequence similarity but display the common feature of inducing two completely opposite
intracellular signals depending on ligand availability: in the presence of ligand, these receptors transduce a
positive signal leading to survival, differentiation or migration, while in the absence of ligand, the receptors
initiate or amplify a negative signal for apoptosis. Thus, cells that express these proteins manifest a state of
dependence on their respective ligands. The mechanisms that trigger cell death induction in the absence of ligand
are in large part unknown, but typically require cleavage by specific caspases. In this review we will present the
proposed mechanisms for cell death induction by these receptors and their potential function in nervous system
development and regulation of tumorigenesis.Received 19 December 2003; received after revision 19 February 2004; accepted 26 February 2004 相似文献
5.
Bornberg-Bauer E Beaussart F Kummerfeld SK Teichmann SA Weiner J 《Cellular and molecular life sciences : CMLS》2005,62(4):435-445
Proteins are composed of domains, which are conserved evolutionary units that often also correspond to functional units and can frequently be detected with reasonable reliability using computational methods. Most proteins consist of two or more domains, giving rise to a variety of combinations of domains. Another level of complexity arises because proteins themselves can form complexes with small molecules, nucleic acids and other proteins. The networks of both domain combinations and protein interactions can be conceptualised as graphs, and these graphs can be analysed conveniently by computational methods. In this review we summarise facts and hypotheses about the evolution of domains in multi-domain proteins and protein complexes, and the tools and data resources available to study them.Received 20 September 2004; received after revision 23 October 2004; accepted 1 November 2004 相似文献
6.
Sarramegn V Muller I Milon A Talmont F 《Cellular and molecular life sciences : CMLS》2006,63(10):1149-1164
G protein-coupled receptors (GPCRS) represent a class of integral membrane proteins involved in many biological processes
and pathologies. Fifty percent of all modern drugs and almost 25% of the top 200 bestselling drugs are estimated to target
GPCRs. Despite these crucial biological implications, very little is known, at atomic resolution, about the detailed molecular
mechanisms by which these membrane proteins are able to recognize their extra-cellular stimuli and transmit the associated
messages. Obviously, our understanding of GPCR functioning would be greatly facilitated by the availability of high-resolution
three-dimensional (3D) structural data. However, expression, solubilization and purification of these membrane proteins are
not easy to achieve, and at present, only one 3D structure has been determined, that of bovine rhodopsin. This review presents
and compares the different successful strategies which have been applied to solubilize and purify recombinant GPCRs in the
perspective of structural biology experiments.
Received 21 November 2005; received after revision 20 January 2006; accepted 2 February 2006
An erratum to this article is available at . 相似文献
7.
Vesicle fusion is a ubiquitous biological process involved in membrane trafficking and a variety of specialised events such
as exocytosis and neurite outgrowth. The energy to drive biological membrane fusion is provided by fusion proteins called
SNAREs. Indeed, SNARE proteins play critical roles in neuronal development as well as neurotransmitter and hormone release.
SNARE proteins form a very tight alpha-helical bundle that can pull two membranes together, thereby initiating fusion. Whereas
a great deal of attention has been paid to partner proteins that can affect SNARE function, recent genetic and biochemical
evidence suggests that local lipid environment may be as important in SNARE regulation. Direct lipid modification of SNARE
fusion proteins and their regulation by fatty acids following phospholipase action will be discussed here in detail. Our analysis
highlights the fact that lipids are not a passive platform in vesicle fusion but intimately regulate SNARE function.
Received 20 December 2006; received after revision 6 February 2007; accepted 15 March 2007 相似文献
8.
Plant pathogenic bacteria inject about 30 virulence effector proteins into the host cell using a specialized secretion apparatus.
Bacteria which are unable to do this elicit host immunity and cannot grow inside living plant tissue. Thus, the primary function
of the effectors is to suppress host immunity. The identity of individual effectors within each complement varies even between
closely related bacterial strains, and effectors themselves act redundantly and are apparently interchangeable. Many effectors
are known to target components of plant defense pathways, but it is difficult to study their role in molecular terms. For
some of them, there is controversy about their mode of action. We propose that effectors act promiscuously by targeting host
molecules with low specificity and affinity. 相似文献
9.
Long alpha-helical coiled-coil proteins are involved in a variety of organizational and regulatory processes in eukaryotic cells. They provide cables and networks in the cyto- and nucleoskeleton, molecular scaffolds that organize membrane systems, motors, levers, rotating arms and possibly springs. A growing number of human diseases are found to be caused by mutations in long coiled-coil proteins. This review summarizes our current understanding of the multifaceted group of long coiled-coil proteins in the cytoskeleton, nucleus, Golgi and cell division apparatus. The biophysical features of coiled-coil domains provide first clues toward their contribution to the diverse protein functions and promise potential future applications in the area of nanotechnology. Combining the power of fully sequenced genomes and structure prediction algorithms, it is now possible to comprehensively summarize and compare the complete inventory of coiled-coil proteins of different organisms.Received 27 January 2004; received after revision 23 February 2004; accepted 10 March 2004 相似文献
10.
R. T. Allen M. W. Cluck D. K. Agrawal 《Cellular and molecular life sciences : CMLS》1998,54(5):427-445
Apoptosis is an essential and highly conserved mode of cell death that is important for normal development, host defense
and suppression of oncogenesis. Faulty regulation of apoptosis has been implicated in degenerative conditions, vascular diseases,
AIDS and cancer. Among the numerous proteins and genes involved, members of the Bcl-2 family play a central role to inhibit
or promote apoptosis. In this article, we present up-to-date information and recent discoveries regarding biochemical functions
of Bcl-2 family proteins, positive and negative interactions between these proteins, and their modification and regulation
by either proteolytic cleavage or by cytosolic kinases, such as Raf-1 and stress-activated protein kinases. We have critically
reviewed the functional role of caspases and the consequences of cleaving key substrates, including lamins, poly(ADP ribose)
polymerase and the Rb protein. In addition, we have presented the latest Fas-induced signalling mechanism as a model for receptor-linked
caspase regulation. Finally, the structural and functional interactions of Ced-4 and its partial mam malian homologue, apoptosis
protease activating factor-1 (Apaf-1), are presented in a model which includes other Apafs. This model culminates in a caspase/Apaf
regulatory cascade to activate the executioners of programmed cell death following cytochrome c release from the mitochondria
of mammalian cells. The importance of these pathways in the treatment of disease is highly dependent on further characterization
of genes and other regulatory molecules in mammals.
Received 18 February 1998; accepted February 1998 相似文献
11.
Lethal toxin (LT) is a major virulence factor secreted by anthrax bacteria. It is composed of two proteins, PA (protective antigen) and LF (lethal factor). PA transports the LF inside the cell, where LF, a zinc-dependent metalloprotease cleaves the mitogen activated protein kinase kinase (MAPKK) enzymes of the mitogen activated protein kinase (MAPK) signaling pathway, thereby impairing their function. This disruption of the MAPK pathway, which serves essential functions such as proliferation, survival and inflammation in all cell types, results in multisystem dysfunction in the host. The inactivation of the MAPK pathway in both macrophages and dendritic cells leads to inhibition of proinflammatory cytokine secretion, downregulation of costimulatory molecules such as CD80 and CD86, and ineffective T cell priming. The net result is an impaired innate and adaptive immune response. Endothelial cells of the vascular system undergo apoptosis upon LT exposure, also likely due to inactivation of the MAPK pathway. The activity of various hormone receptors such as glucocorticoids, progesterone and estrogen is also blocked, due to inhibition of p38 MAPK phosphorylation, thus affecting the bodys response to stress. The present review summarizes the various disarming effects of Bacillus anthracis through the use of a single weapon, the lethal toxin.Received 12 June 2004; received after revision 13 July 2004; accepted 28 July 2004 相似文献
12.
Reactive oxygen species (ROS) production by the phagocyte NADPH oxidase is essential for host defenses against pathogens. ROS are very reactive with biological molecules such as lipids, proteins and DNA, potentially resulting in cell dysfunction and tissue insult. Excessive NADPH oxidase activation and ROS overproduction are believed to participate in disorders such as joint, lung, vascular and intestinal inflammation. NADPH oxidase is a complex enzyme composed of six proteins: gp91phox (renamed NOX2), p22phox, p47phox, p67phox, p40phox and Rac1/2. Inhibitors of this enzyme could be beneficial, by limiting ROS production and inappropriate inflammation. A few small non-peptide inhibitors of NADPH oxidase are currently used to inhibit ROS production, but they lack specificity as they inhibit NADPH oxidase homologues or other unrelated enzymes. Peptide inhibitors that target a specific sequence of NADPH oxidase components could be more specific than small molecules. Here we review peptide-based inhibitors, with particular focus on a molecule derived from gp91phox/NOX2 and p47phox, and discuss their possible use as specific phagocyte NADPH oxidase inhibitors. 相似文献
13.
Rab proteins are members of the Ras superfamily of GTPases and are key regulators of intracellular vesicular transport. They undergo a cycle of GTPase activity, and this activity is interconnected to a cycle of reversible attachment to membranes. This cycle is mediated by geranylgeranylation of (usually) two C-terminal cysteines, which in turn is effected by Rab geranylgeranyltransferase in concert with REP (Rab escort protein). After delivery to their respective membranes, Rabs are activated by replacement of GDP by GTP, allowing interaction with a wide variety of effector molecules involved in vesicular transport, in particular with docking of transport vesicles to their specific target membranes. After completion of these events and GTP hydrolysis, Rabs are retrieved by GDI (GDP dissociation inhibitor) and delivered to their starting compartment. Here, the structural and mechanistic basis of events occurring in Rab delivery and cycling, and the differences between REP and GDI are discussed on the basis of recent advances in the field.Received 4 November 2004; received after revision 14 February 2005; accepted 31 March 2005 相似文献
14.
V. Bellotti P. Mangione M. Stoppini 《Cellular and molecular life sciences : CMLS》1999,55(6-7):977-991
The physiological metabolism of proteins guarantees that different cellular compartments contain the appropriate concentration
of proteins to perform their biological functions and, after a variable period of wear and tear, mediates their natural catabolism.
The equilibrium between protein synthesis and catabolism ensures an effective turnover, but hereditary or acquired abnormalities
of protein structure can provoke a premature loss of biological function, an accelerated catabolism and diseases caused by
the loss of an irreplaceable function. In certain proteins, abnormal structure and metabolism are associated with a strong
tendency to self-aggregation into a polymeric fibrillar structure, and in these cases the disease is not principally caused
by the loss of an irreplaceable function but by the action of this new biological entity. Amyloid fibrils are an apparently
inert, insoluble, mainly extracellular protein polymer that kills the cell without tissue necrosis but by activation of the
apoptotic mechanism. We analyzed the data reported so far on the structural and functional properties of four prototypic proteins
with well-known biological functions (lysozyme, transthyretin, β2-microglobulin and apolipoprotein AI) that are able to create
amyloid fibrils under certain conditions, with the perspective of evaluating whether the achievement of biological function
favors or inhibits the process of fibril formation. Furthermore, studying the biological functions carried out by amyloid
fibrils reveals new types of protein-protein interactions in the transmission of messages to cells and may provide new ideas
for effective therapeutic strategies.
Received 9 November 1998; received after revision 15 January 1999; accepted 15 January 1999 相似文献
15.
Summary Intraperitoneal aggregation of leucocytes is produced in an identical manner by intraperitoneal application of different amounts of living and dead bacteria and bacterial products. The maximum accumulation occurs with medium dosages of bacteria or their products, with high dosages no leucocytic accumulation is produced. Pretreatment with selected LPS of bacteria enhances the intraperitoneal accumulation of leucocytes also with the high amounts of bacteria, whereas the reaction in not pretreated with LPS is suppressed. Parallel to the increase of the intraperitoneal leucocytic accumulation the animals are protected against the infection with high amounts of bacteria, to which they succumb if not pretreated with LPS. 相似文献
16.
The facultative intracellular pathogen Salmonella enterica resides in a special membrane compartment of the host cell and modifies its host to achieve intracellular survival and proliferation. The type III secretion system encoded by Salmonella pathogenicity island 2 (SPI2) has a central role in the interference of intracellular Salmonella with host cell functions. SPI2 function affects antimicrobial defense mechanisms of the host, intracellular transport processes, integrity and function of the cytoskeleton and host cell death. These modifications are mediated by translocation of a large number of effector proteins by the SPI2 system. In this review, we summarize recent work on the cellular phenotypes related to SPI2 function and contribution of SPI2 effector proteins to these manipulations. These studies reveal a complex set of pathogenic interferences between intracellular Salmonella and its host cells.Received 11 June 2004; received after revision 8 July 2004; accepted 12 July 2004 相似文献
17.
Periplasmic lysozyme inhibitor contributes to lysozyme resistance in <Emphasis Type="Italic">Escherichia coli</Emphasis> 总被引:1,自引:1,他引:0
Deckers D Masschalck B Aertsen A Callewaert L Van Tiggelen CG Atanassova M Michiels CW 《Cellular and molecular life sciences : CMLS》2004,61(10):1229-1237
The product of the Escherichia coli ORFan gene ykfE was recently shown to be a strong inhibitor of C-type lysozyme in vitro. The gene was correspondingly renamed ivy (inhibitor of vertebrate lysozyme), but its biological function in E. coli remains unknown. In this work, we investigated the role of Ivy in the resistance of E. coli to the bactericidal effect of lysozyme in the presence of outer-membrane-permeabilizing treatments. Both in the presence of lactoferrin (3.0 mg/ml) and under high hydrostatic pressure (250 MPa), the lysozyme resistance of E. coli MG1655 was decreased by knock-out of Ivy, and increased by overexpression of Ivy. However, knock-out of Ivy did not increase the lysozyme sensitivity of an E. coli MG1655 mutant previously described to be resistant to lysozyme under high pressure. These results indicate that Ivy is one of several factors that affect lysozyme resistance in E. coli, and suggest a possible function for Ivy as a host interaction factor in commensal and pathogenic E. coli.Received 12 February 2004; received after revision 11 March 2004; accepted 16 March 2004 相似文献
18.
Pili in Gram-negative and Gram-positive bacteria — structure, assembly and their role in disease 总被引:2,自引:0,他引:2
Many bacterial species possess long filamentous structures known as pili or fimbriae extending from their surfaces. Despite
the diversity in pilus structure and biogenesis, pili in Gram-negative bacteria are typically formed by non-covalent homopolymerization
of major pilus subunit proteins (pilins), which generates the pilus shaft. Additional pilins may be added to the fiber and
often function as host cell adhesins. Some pili are also involved in biofilm formation, phage transduction, DNA uptake and
a special form of bacterial cell movement, known as ‘twitching motility’ In contrast, the more recently discovered pili in
Gram-positive bacteria are formed by covalent polymerization of pilin subunits in a process that requires a dedicated sortase
enzyme. Minor pilins are added to the fiber and play a major role in host cell colonization.
This review gives an overview of the structure, assembly and function of the best-characterized pili of both Gram-negative
and Gram-positive bacteria.
Received 08 August 2008; received after revision 24 September 2008; accepted 01 October 2008 相似文献
19.
Lamarine M Mornon JP Berezovsky N Chomilier J 《Cellular and molecular life sciences : CMLS》2001,58(3):492-498
Using a set of 372 proteins representative of a variety of 56 distinct globular folds, a statistical correlation was observed
between two recently revealed features of protein structures: tightened end fragments or 'closed loops', i. e. sequence fragments
that are able in three-dimensional (3D) space to nearly close their ends (a current parameter of polymer physics), and 'topohydrophobic
positions', i. e. positions always occupied in 3D space by strong hydrophobic amino acids for all members of a fold family.
Indeed, in sequence space, the distribution of preferred lengths for tightened end fragments and that for topohydrophobic
separation match. In addition to this statistically significant similarity, the extremities of these 'closed loops' may be
preferentially occupied by topohydrophobic positions, as observed on a random sample of various folds. This observation may
be of special interest for sequence comparison of distantly related proteins. It is also important for the ab initio prediction
of protein folds, considering the remarkable topological properties of topohydrophobic positions and their paramount importance
within folding nuclei. Consequently, topohydrophobic positions locking the 'closed loops' belong to the deep cores of protein
domains and might have a key role in the folding process.
Received 1 February 2001; accepted 7 February 2001 相似文献
20.
Orange JS Stone KD Turvey SE Krzewski K 《Cellular and molecular life sciences : CMLS》2004,61(18):2361-2385
The Wiskott-Aldrich Syndrome (WAS) is an inherited immunodeficiency caused by a variety of mutations in the gene encoding the WAS protein (WASp). WASp is expressed in hematopoetic cells and facilitates the reorganization of the actin cytoskeleton in response to many important cell stimuli. Extensive study of WAS and more recently WASp has given great insight into the relevance of this molecule and related molecules to both basic cell biology and human immune defenses.Received 28 February 2004; received after revision 15 April 2004; accepted 26 April 2004 相似文献