Team "Protein-Glycosaminoglycan Interactions"

Aims:

To analyse the structural determinant involved in Protein-Glycoaminoglycan recognition process. To understand the mechanism by wich glycoaminoglycans modify the structure and the reactivity of the proteins they bind.

Topics:

• Regulation of cytokine and chemokine activities by heparan sulfate.
• Role of heparan sulfate in the cellular attachment process of infectious agents.
• Glycoaminoglycans structure and regulation
• Methodological developments (GAG-on-chips)

Key words:

Oligosaccharidse, Glycosaminoglycans, Heparan sulfate, Cytokine/Chemokine, Infectious agents, Receptor, Immunity/Inflammation, Biosynthesis, Mechanism of internalization, Interactions.

Specialized techniques:

Kinetic analysis of binding reactions (BIAcore technology)
Glycosaminoglycan sequencing
Peptide sequencing of the protein-glycoaminoglycan interface

Major publications:

Lortat-Jacob H., Grosdidier A. & Imberty A. (2002) Structural diversity of heparan sulfate binding domains in chemokines. Proc. Natl. Acad. Sci. USA 99, 1229-1234.

Reeves E.P., Lu H., Lortat-Jacob H., Messina C.G.M., Bolsover S., Gabella G., Potma E.O.,Warley A., Roes J. & Segal A.W. (2002) Killing activity of neutrophils is mediated through activation of proteases by K+ flux. Nature 416, 291-297.

Halary F, Amara A, Lortat-Jacob H, Messerle M, Delaunay T, Houles C, Fieschi F, Arenzana-Seisdedos F, Moreau JF, & Dechanet-Merville J. (2002) Human Cytomegalovirus Binding to DC-SIGN Is Required for Dendritic Cell Infection and Target Cell trans-Infection. Immunity 17, 653-664

Sadir R., Imberty A., Baleux F. & Lortat-Jacob H. (2004) Heparan sulfate / heparin oligosaccharides protect stromal cell-derived factor-1 (SDF-1)/CXCL12 against proteolysis induced by CD26/dipeptidyl peptidase IV. J. Biol Chem. 279, 43854-43860.

Vivès R.R, Crublet E, Andrieu J.-P., Gagnon J., Rousselle P., & Lortat-Jacob H. (2004) A novel strategy for defining critical amino acid residues involved in protein/GAG interactions. J. Biol. Chem. 279, 54327-54333.

Sarrazin S., Bonnaffé D., Lubineau A. & Lortat-Jacob H (2005) Heparan sulfate mimicry: A synthetic glycoconjugate that recognizes the heparin-binding domain of IFNg inhibits the cytokine activity. J. Biol. Chem. 280, 37558-37564.

Vivès R.R, Imberty A., Sattentau Q.J. & Lortat-Jacob H. (2005) Heparan sulfate targets the HIV-1 envelope glycoprotein gp120 coreceptor binding site.J. Biol. Chem. 280, 21353-21357.