Large-scale investigation of Leishmania interaction networks with host extracellular matrix by surface plasmon resonance imaging.

We have set up an assay to study the interactions of live pathogens with their hosts by using protein and glycosaminoglycan arrays probed by surface plasmon resonance imaging. We have used this assay to characterize the interactions of Leishmania promastigotes with ~70 mammalian host biomolecules (extracellular proteins, glycosaminoglycans, growth factors, cell surface receptors). We have identified, in total, 27 new partners (23 proteins, 4 glycosaminoglycans) of procyclic promastigotes of six Leishmania species and 18 partners (15 proteins, 3 glycosaminoglycans) of three species of stationary-phase promastigotes for all the strains tested.

Heparin-protein interactions: from affinity and kinetics to biological roles. Application to an interaction network regulating angiogenesis.

Numerous extracellular proteins, growth factors, chemokines, cytokines, enzymes, lipoproteins, involved in a variety of biological processes, interact with heparin and/or heparan sulfate at the cell surface and in the extracellular matrix (ECM). The goal of this study is to investigate the relationship(s) between affinity and kinetics of heparin-protein interactions and the localization of the proteins, their intrinsic disorder and their biological roles. Most proteins bind to heparin with a higher affinity than their fragments and form more stable complexes with heparin than with heparan sulfate.

Extended interaction network of procollagen C-proteinase enhancer-1 in the extracellular matrix.

PCPE-1 (procollagen C-proteinase enhancer-1) is an extracellular matrix glycoprotein that can stimulate procollagen processing by procollagen C-proteinases such as BMP-1 (bone morphogenetic protein 1). PCPE-1 interacts with several proteins in addition to procollagens and BMP-1, suggesting that it could be involved in biological processes other than collagen maturation. We thus searched for additional partners of PCPE-1 in the extracellular matrix, which could provide new insights into its biological roles.

Comparative analysis of Leishmania exoproteomes: implication for host-pathogen interactions.

Leishmaniasis is a vector-borne disease caused by the protozoa Leishmania. We have analyzed and compared the sequences of three experimental exoproteomes of Leishmania promastigotes from different species to determine their specific features and to identify new candidate proteins involved in interactions of Leishmania with the host. The exoproteomes differ from the proteomes by a decrease in the average molecular weight per protein, in disordered amino acid residues and in basic proteins.

Intrinsic disorder of the extracellular matrix.

The extracellular matrix is very well organized at the supramolecular and tissue levels and little is known on the potential role of intrinsic disorder in promoting its organization. We predicted the amount of disorder and identified disordered regions in the human extracellular proteome with established computational tools. The extracellular proteome is significantly enriched in proteins comprising more than 50% of disorder compared to the complete human proteome.

Understanding the biology of aging with interaction networks.

Aging is a multifactorial phenomenon, a multiscale process that takes place at the molecular (proteins, genes), cellular and tissue levels and represents a complex set of events. This review will focus on the databases related to the aging process and on aging-related biological networks recently constructed to decipher the molecular mechanisms of aging, to characterize the effects of environmental factors and calorie restriction on aging and to determine the molecular links between aging and several diseases. The role played by chaperones, that are major participants of aging cellular networks and connect metabolic stress and dietary restriction, and by microRNAs as modulators of aging are discussed.