Plasticity of the β-Trefoil Protein Fold in the Recognition and Control of Invertebrate Predators and Parasites by a Fungal Defence System

Discrimination between self and non-self is a prerequisite for any defence mechanism; in innate defence, this discrimination is often mediated by lectins recognizing non-self carbohydrate structures and so relies on an arsenal of host lectins with different specificities towards target organism carbohydrate structures. Recently, cytoplasmic lectins isolated from fungal fruiting bodies have been shown to play a role in the defence of multicellular fungi against predators and parasites. Here, we present a novel fruiting body lectin, CCL2, from the ink cap mushroom Coprinopsis cinerea. We demonstrate the toxicity of the lectin towards Caenorhabditis elegans and Drosophila melanogaster and present its NMR solution structure in complex with the trisaccharide, GlcNAcβ1,4[Fucα1,3]GlcNAc, to which it binds with high specificity and affinity in vitro. The structure reveals that the monomeric CCL2 adopts a β-trefoil fold and recognizes the trisaccharide by a single, topologically novel carbohydrate-binding site. Site-directed mutagenesis of CCL2 and identification of C. elegans mutants resistant to this lectin show that its nematotoxicity is mediated by binding to α1,3-fucosylated N-glycan core structures of nematode glycoproteins; feeding with fluorescently labeled CCL2 demonstrates that these target glycoproteins localize to the C. elegans intestine. Since the identified glycoepitope is characteristic for invertebrates but absent from fungi, our data show that the defence function of fruiting body lectins is based on the specific recognition of non-self carbohydrate structures. The trisaccharide specifically recognized by CCL2 is a key carbohydrate determinant of pollen and insect venom allergens implying this particular glycoepitope is targeted by both fungal defence and mammalian immune systems. In summary, our results demonstrate how the plasticity of a common protein fold can contribute to the recognition and control of antagonists by an innate defence mechanism, whereby the monovalency of the lectin for its ligand implies a novel mechanism of lectin-mediated toxicity

Saving-investment relationship, financial crisis and structural changes in East Asian countries.

http://www.cepii.fr/anglaisgraph/publications/economieinter/rev111/bautista.pdfIn this article, the impact of the Asian crisis on the saving-investment relationship of selected East Asian countries with the rest of the world is examined using a Markov switching regression on East Asian countries. As a first result, estimates of the saving retention coefficients show that for most Asian countries, the Asian crisis period marks a shift from high saving retention coefficients during the pre-crisis period to low ones up to the end of the sample period. Low saving retention coefficients are also observed during the 1980s decade. For some countries, these coincide with certain phases of their development. A second result of interest is that periods with relatively low coefficient estimates, implying relatively higher capital mobility, are associated with current account surpluses. This result can be more explained by high and stable domestic saving rates than by low investment rates.Dans cet article, nous examinons l'impact de la crise asiatique sur la relation épargne-investissement des pays asiatiques avec le reste du monde. Pour ce faire, nous appliquons la méthode dite de Markov-switching aux principaux pays d'Asie du Sud Est. Le premier résultat de notre étude est le fait que la crise asiatique s'est accompagnée d'une réduction significative de la corrélation entre l'épargne et l'investissement pour la plupart des pays asiatiques. Ces faibles coefficients sont également observés pendant la décennie des années 80, période caractérisée par une phase de développement importante. Notre second résultat est paradoxal : pendant les périodes où les coefficients de rétention sont faibles, i.e. où la mobilité du capital est relativement élevée, les soldes du compte courant sont positifs. Ce résultat s'explique principalement par de forts taux d'épargne nationaux plutôt que par de faibles taux d'investissement

Saving-Investment Relationship, Financial Crisis and Structural Changes in East Asian Countries

In this article, the impact of the Asian crisis on the saving-investment relationship of selected East Asian countries with the rest of the world is examined using a Markov switching regression on East Asian countries. As a first result, estimates of the saving retention coefficients show that for most Asian countries, the Asian crisis period marks a shift from high saving retention coefficients during the pre-crisis period to low ones up to the end of the sample period. Low saving retention coefficients are also observed during the 1980s decade. For some countries, these coincide with certain phases of their development. A second result of interest is that periods with relatively low coefficient estimates, implying relatively higher capital mobility, are associated with current account surpluses. This result can be more explained by high and stable domestic saving rates than by low investment rates.Saving-investment relationship; financial integration; asian crisis; markov-switching model

Quand la réponse banale devient singulière

Rebourg Christine, Vivot Martine, Biessy-Maveyraud C., Carreras N. Quand la réponse banale devient singulière. In: Bulletin de la Société française du Rorschach et des méthodes projectives, n°38, 1994. pp. 137-142

Quantitative comparison of catalytic mechanisms and overall reactions in convergently evolved enzymes : implications for classification of enzyme function

The authors thank the National Institutes of Health (NIH R01 GM60595 to PCB) and the Scottish Universities Life Sciences Alliance (SULSA to JBOM) for funding.Functionally analogous enzymes are those that catalyze similar reactions on similar substrates but do not share common ancestry, providing a window on the different structural strategies nature has used to evolve required catalysts. Identification and use of this information to improve reaction classification and computational annotation of enzymes newly discovered in the genome projects would benefit from systematic determination of reaction similarities. Here, we quantified similarity in bond changes for overall reactions and catalytic mechanisms for 95 pairs of functionally analogous enzymes (non-homologous enzymes with identical first three numbers of their EC codes) from the MACiE database. Similarity of overall reactions was computed by comparing the sets of bond changes in the transformations from substrates to products. For similarity of mechanisms, sets of bond changes occurring in each mechanistic step were compared; these similarities were then used to guide global and local alignments of mechanistic steps. Using this metric, only 44% of pairs of functionally analogous enzymes in the dataset had significantly similar overall reactions. For these enzymes, convergence to the same mechanism occurred in 33% of cases, with most pairs having at least one identical mechanistic step. Using our metric, overall reaction similarity serves as an upper bound for mechanistic similarity in functional analogs. For example, the four carbon-oxygen lyases acting on phosphates (EC 4.2.3) show neither significant overall reaction similarity nor significant mechanistic similarity. By contrast, the three carboxylic-ester hydrolases (EC 3.1.1) catalyze overall reactions with identical bond changes and have converged to almost identical mechanisms. The large proportion of enzyme pairs that do not show significant overall reaction similarity (56%) suggests that at least for the functionally analogous enzymes studied here, more stringent criteria could be used to refine definitions of EC sub-subclasses for improved discrimination in their classification of enzyme reactions. The results also indicate that mechanistic convergence of reaction steps is widespread, suggesting that quantitative measurement of mechanistic similarity can inform approaches for functional annotation.Publisher PDFPeer reviewe

Evolution to carbapenem-hydrolyzing activity in noncarbapenemase class D β-lactamase OXA-10 by rational protein design

Class D β-lactamases with carbapenemase activity are emerging as carbapenem-resistance determinants in Gram-negative bacterial pathogens, mostly Acinetobacter baumannii and Klebsiella pneumoniae. Carbapenemase activity is an unusual feature among class D β-lactamases, and the structural elements responsible for this activity remain unclear. Based on structural and molecular dynamics data, we previously hypothesized a potential role of the residues located in the short-loop connecting strands β5 and β6 (the β5–β6 loop) in conferring the carbapenemase activity of the OXA-48 enzyme. In this work, the narrow-spectrum OXA-10 class D β-lactamase, which is unable to hydrolyze carbapenems, was used as a model to investigate the possibility of evolving carbapenemase activity by replacement of the β5–β6 loop with those present in three different lineages of class D carbapenemases (OXA-23, OXA-24, and OXA-48). Biological assays and kinetic measurements showed that all three OXA-10–derived hybrids acquired significant carbapenemase activity. Structural analysis of the OXA-10loop24 and OXA-10loop48 hybrids revealed no significant changes in the molecular fold of the enzyme, except for the orientation of the substituted β5–β6 loops, which was reminiscent of that found in their parental enzymes. These results demonstrate the crucial role of the β5–β6 loop in the carbapenemase activity of class D β-lactamases, and provide previously unexplored insights into the mechanism by which these enzymes can evolve carbapenemase activity