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The ins and outs of matrix : molecules, enzymes and viruses

Vendredi 8 juin 2018 11:00 - Duree : 1 heure
Lieu : Salle des séminaires de l’IBS - 71, avenue des Martyrs - Grenoble

Orateur : Dave FERNIG (Department of Biochemistry, Biosciences Building, University of Liverpool, UK)

The extracellular matrix is the medium through which metazoan cells communicate by means of soluble effectors and mechanical forces. Consequently, it is functionally at the heart of the integration of cell function within organs and between organs. Thus, extracellular matrix contributes to the fundamental biological difference between multicellular and unicellular animals : natural selection in the former acts on the organism, rather than the individual cell. At the molecular level, the human extracellular proteome, including that of the extracellular matrix is the most connected (through protein-protein interactions) of all the proteomes. These interaction analyses, however, overlook the elephant in the room : the glycosaminoglycans, sulfated polysaccharides, which interact with at least 850 different extracellular protein species. Such data point to the glycosaminoglycans in general and heparan sulfate in particular, as being central to the regulation of cell communication. The selectivity and specificity of protein interactions with glycosaminoglycans is the subject of a long-standing argument. However, as our work shows, these arguments may be misplaced : the interactions are graded and at the molecular level, often multivalent and result in a robust control of information flow. There are major opportunities for the development of treatments for diseases of major socio-economic impact. One example is Alzheimer’s, where the aberrant production of a particular heparan sulfate structure drives its accumulation inside neurons and where it triggers taupathy. Infectious diseases, including ones caused by viruses (‘flu, dengue, zika) and by parasites (malaria leishmaniasis) are another example. In terms of molecular recognition, protein-glycosaminoglycan interactions are usually ‘fixed’ and do not seem capable of much evolution. This may be the consequence of the complexity of the system : heparan sulfate biosynthesis, for example, has to accommodate interactions with hundreds of different proteins and be able to distinguish between these. Consequently, heparan sulfate may be our Achilles’ heel : we cannot enter into an evolutionary race with a pathogen that employs heparan sulfate as part of its invasion/replication strategy. This weakness opens up the possibility of exploitation of the pathogen-sulfate interaction therapeutically.

Contact : ibs.seminaires@ibs.fr

Discipline évènement : (Biologie / Chimie)
Entité organisatrice : (IBS)
Nature évènement : (Séminaire)
Evènement répétitif : (Séminaire IBS)
Site de l'évènement : Polygone scientifique

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