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171.
Sauvion N Nardon C Febvay G Gatehouse AM Rahbé Y 《Journal of insect physiology》2004,50(12):1137-1150
Concanavalin A (lectin from Canavalia ensiformis L., ConA) has previously been shown to act as a feeding inhibitor for Acyrthosiphon pisum, the pea aphid. In the present study a range of histochemical and biochemical techniques were used to elucidate the target tissues and binding sites of the lectin in the aphid. Diet uptake was evaluated using a radioactive tracer (14C-methylated inulin) and demonstrated that adults were capable of ingesting high quantities of the toxin (approx. 1 μg over a 48 h period). Electophoretic analysis and enzyme-linked immuno-sorbent assay of honeydew samples confirmed these results and further demonstrated that only small levels of ConA were excreted. Histofluorescence and immunolocalisation studies on nymphs revealed that the stomach was the primary target for ConA. At concentrations up to 400 μg ml−1, lectin binding only occurred in the stomach region, however, at high concentrations (800 μg ml−1) the whole digestive tract was stained, although there was no evidence of binding in either the oesophagus or rectum. In addition to binding, there was evidence to suggest that ConA was also causing systemic effects in that the lectin appeared to cross the intestinal epithelial barrier. Immunohistochemical and electron microscopy studies revealed that ConA induced severe cellular swelling of the epithelial cells, accompanied by hypersecretion and a progressive detachment of the apical membrane; however, the striated border itself did not appear to be directly affected. Furthermore, there was no lysis of the epithelium, nor loss of integrity of the epithelial cells themselves. Our results suggest that ConA interacts with glycosylated receptors at the surface of the stomach epithetial cells, interfering with normal metabolism and cell function, resulting in a rapid feedback response on feeding behaviour. Whilst our results provide a much greater understanding regarding the modes of action of ConA in insects, they suggest that different lectins, including other mannose binding lectins, have different modes of action at the cellular levels, and thus generalizations should be treated with caution. 相似文献
172.
Loris R Van Walle I De Greve H Beeckmans S Deboeck F Wyns L Bouckaert J 《Journal of molecular biology》2004,335(5):1227-1240
The crystal structure of a Man/Glc-specific lectin from the seeds of the bloodwood tree (Pterocarpus angolensis), a leguminous plant from central Africa, has been determined in complex with mannose and five manno-oligosaccharides. The lectin contains a classical mannose-specificity loop, but its metal-binding loop resembles that of lectins of unrelated specificity from Ulex europaeus and Maackia amurensis. As a consequence, the interactions with mannose in the primary binding site are conserved, but details of carbohydrate-binding outside the primary binding site differ from those seen in the equivalent carbohydrate complexes of concanavalin A. These observations explain the differences in their respective fine specificity profiles for oligomannoses. While Man(alpha1-3)Man and Man(alpha1-3)[Man(alpha1-6)]Man bind to PAL in low-energy conformations identical with that of ConA, Man(alpha1-6)Man is required to adopt a different conformation. Man(alpha1-2)Man can bind only in a single binding mode, in sharp contrast to ConA, which creates a higher affinity for this disaccharide by allowing two binding modes. 相似文献
173.
Birck C Damian L Marty-Detraves C Lougarre A Schulze-Briese C Koehl P Fournier D Paquereau L Samama JP 《Journal of molecular biology》2004,344(5):1409-1420
A newly defined family of fungal lectins displays no significant sequence similarity to any protein in the databases. These proteins, made of about 140 amino acid residues, have sequence identities ranging from 38% to 65% and share binding specificity to N-acetyl galactosamine. One member of this family, the lectin XCL from Xerocomus chrysenteron, induces drastic changes in the actin cytoskeleton after sugar binding at the cell surface and internalization, and has potent insecticidal activity. The crystal structure of XCL to 1.4 A resolution reveals the architecture of this new lectin family. The fold of the protein is not related to any of the several lectin folds documented so far. Unexpectedly, the structure similarity is significant with actinoporins, a family of pore-forming toxins. The specific structural features and sequence signatures in each protein family suggest a potential sugar binding site in XCL and a possible evolutionary relationship between these proteins. Finally, the tetrameric assembly of XCL reveals a complex network of protomer-protomer interfaces and generates a large, hydrated cavity of 1000 A3, which may become accessible to larger solutes after a small conformational change of the protein. 相似文献
174.
Artocarpin, a tetrameric lectin of molecular mass 65 kDa, is one of the two lectins extracted from the seeds of jackfruit. The structures of the complexes of artocarpin with mannotriose and mannopentose reported here, together with the structures of artocarpin and its complex with Me-alpha-mannose reported earlier, show that the lectin possesses a deep-seated binding site formed by three loops. The binding site can be considered as composed of two subsites; the primary site and the secondary site. Interactions at the primary site composed of two of the loops involve mainly hydrogen bonds, while those at the secondary site comprising the third loop are primarily van der Waals in nature. Mannotriose in its complex with the lectin interacts through all the three mannopyranosyl residues; mannopentose interacts with the protein using at least three of the five mannose residues. The complexes provide a structural explanation for the carbohydrate specificities of artocarpin. A detailed comparison with the sugar complexes of heltuba, the only other mannose-specific jacalin-like lectin with known three-dimensional structure in sugar-bound form, establishes the role of the sugar-binding loop constituting the secondary site, in conferring different specificities at the oligosaccharide level. This loop is four residues longer in artocarpin than in heltuba, providing an instance where variation in loop length is used as a strategy for generating carbohydrate specificity. 相似文献
175.
176.
177.
Quantitative trait loci for IQ and other complex traits: single-nucleotide polymorphism genotyping using pooled DNA and microarrays 总被引:1,自引:0,他引:1
Similar to other complex traits, it is likely that many DNA polymorphisms of small effect size [quantitative trait loci (QTLs)] are responsible for the high heritability of intelligence, in addition to many rare monogenic disorders known to contribute to lowered intelligence. We review the current status of approaches to identify QTLs associations for intelligence employing genome-wide strategies using pooled DNA from many individuals and evaluate the innovative approach of microarray analysis to genotype DNA pools for large numbers of single nucleotide polymorphisms. 相似文献
178.
Rho kinase (ROCK) may play an important role in regulating biological events of cells, including proliferation, differentiation and survival/death. Blockade of ROCK promotes axonal regeneration and neuron survival in vivo and in vitro, thereby exhibiting potential clinical applications in spinal cord damage and stroke. Our previous studies have demonstrated that Fasudil, a selective ROCK inhibitor, induced neuroprotection in vitro. Here we used an in vivo model of hypoxia/reoxygenation (H/R) injury to examine the neuroprotective effect of Fasudil, and explore its possible mechanism(s) in vivo. H/R resulted in the loss of hippocampal neurons, accompanied by increased apoptosis of neurons in hippocampus. The expression of ROCK II and activity of ROCK in the brain were increased after H/R, and located only in microglia, but not in astrocytes and neurons. The administration of Fasudil inhibited the activity of ROCK in brain tissue and cultured microglia, and protected hippocampal neurons against H/R injury. Further immunohistochemical analysis and cytokine determination revealed that Fasudil inhibited inducible nitric oxide synthase immunoreactivity in microglia and pro-inflammatory factors in brain tissue after H/R, which is consistent with the observation wherein Fasudil reduced the pro-inflammatory factors nitric oxide, IL-1β, IL-6 and TNF-, and increased anti-inflammatory factor IL-10 in cultured microglia under normoxic or hypoxic conditions. Our results indicate that inhibition of ROCK by Fasudil may represent a useful therapeutic perspective by inhibiting microglial inflammatory responses in the CNS. 相似文献
179.
Gerlind Sulzenbacher Willy J. Peumans Els J.M. Van Damme 《Journal of molecular biology》2010,400(4):715-723
A lectin from the phytopathogenic ascomycete Sclerotinia sclerotiorum that shares only weak sequence similarity with characterized fungal lectins has recently been identified. S. sclerotiorum agglutinin (SSA) is a homodimeric protein consisting of two identical subunits of ∼ 17 kDa and displays specificity primarily towards Gal/GalNAc. Glycan array screening indicates that SSA readily interacts with Gal/GalNAc-bearing glycan chains. The crystal structures of SSA in the ligand-free form and in complex with the Gal-β1,3-GalNAc (T-antigen) disaccharide have been determined at 1.6 and 1.97 Å resolution, respectively. SSA adopts a β-trefoil domain as previously identified for other carbohydrate-binding proteins of the ricin B-like lectin superfamily and accommodates terminal non-reducing galactosyl and N-acetylgalactosaminyl glycans. Unlike other structurally related lectins, SSA contains a single carbohydrate-binding site at site α. SSA reveals a novel dimeric assembly markedly dissimilar to those described earlier for ricin-type lectins. The present structure exemplifies the adaptability of the β-trefoil domain in the evolution of fungal lectins. 相似文献
180.
Pedro J. Alcolea Manuel J. Gómez Mercedes Domínguez Vicente Larraga 《International journal for parasitology》2010,40(13):1497-1516
Leishmania infantum is the causative agent of zoonotic visceral leishmaniasis in the Mediterranean Basin. The promastigote and amastigote stages alternate in the life cycle of the parasite, developing inside the sand-fly gut and inside mammalian phagocytic cells, respectively. High-throughput genomic and proteomic analyses have not focused their attention on promastigote development, although partial approaches have been made in Leishmania major and Leishmania braziliensis. For this reason we have studied the expression modulation of an etiological agent of visceral leishmaniasis throughout the life cycle, which has been performed by means of complete genomic microarrays. In the context of constitutive genome expression in Leishmania spp. described elsewhere and confirmed here (5.7%), we found a down-regulation rate of 68% in the amastigote stage, which has been contrasted by binomial tests and includes the down-regulation of genes involved in translation and ribosome biogenesis. These findings are consistent with the hypothesis of pre-adaptation of the parasite to intracellular survival at this stage. 相似文献