Hugues LORTAT-JACOB
April 24 at 11:00
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From: Institut de Biologie Structurale, Grenoble
Will give a seminar entitled:
Glycosaminoglycans: Master regulators of molecular encounters at the cell surface
GAGs are complex polysaccharides, ubiquitously present at the cell surface and within extracellular matrices (ECM). Through their ability to bind a large array of proteins, almost 4000 of which have been identified to date – including most signaling proteins – GAGs regulate key biologic processes at the cell–tissue interface. To do so, GAGs provide scaffolds to ensure that proteins mediating specific functions will be presented at the correct site and time and also impact the stability, the structure and the reactivity of their protein ligands.
During this seminar I will describe how GAGs and chemokines (a family of chemoattractant cytokines) contribute to maintain haptotactic gradients within tissues along which cells can migrate directionally. Using CXCL12 (stromal cell-derived factor 1) as a model system I will show that GAG-chemokine complex also serves additional purposes that go well beyond a simple immobilization process, including controlling receptor recognition and activation.
I will also introduce the notion of specificity in protein-GAG interactions. To understand how protein binding sites can be imprinted along the GAG chain during their biosynthesis I will describe the X-ray crystallographic or CryoEM 3D-structure of several enzymes involved in GAGs polymerization and maturation.
