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Institut de Biologie StructuraleGrenoble / France

Presentation of Lortat-Jacob Team

Scientific activity

The team is developing two lines of research aimed at (1) analyzing the structure-function relationships of protein-glycosaminoglycan interactions, using mainly cytokines or pathogens as experimental models, and (2) characterizing the mechanisms determining the functional oligosaccharide sequences of HS by studying the biosynthetic machinery of these molecules.

Team members

Current members
• Evelyne Gout (IE CNRS)
• Rabia Sadir (IR CEA)
• Rebekka Wild (CR CNRS)
• Thibault Annaval (Post-doc)
• Hugues Lortat-Jacob (DR CNRS)

Alumni
• Bridgette Connell (PhD student ; October 2008 - February 2012)
• Els Saesen (PhD student ; October 2009 - January 2013)
• Cédric Laguri (CR1 CNRS ; 2005-2013)
• Sébastien Bourcier (Post-doc ; January 2011 - December 2013)
• Aurélie Préchoux (Post-doc ; April 2013 - March 2014)
• Linda Djerbal (PhD student ; October 2015-November 2018)

Main publications (2009-2019)

• Debarnot C., Monneau Y.R., Roig-Zamboni V., Delauzun V., Le Narvor C., Richard E., Hénault J., Goulet A., Fadel F., Vivès R.R., Priem B., Bonnaffé D., Lortat-Jacob H., Bourne Y. Structural insights into substrate binding and catalytic mechanism of human heparan sulfate D-glucuronyl C5 epimerase.
Proc. Natl. Acad. Sci. USA 116, 6760-6765 (2019)

• Richter R.P. and Lortat-Jacob H. Ménage à trois with glycosaminoglycans - a serious rendezvous, not a gag !
Current Opinion in Structural Biology 50, 4-6 (2018)

• Monneau Y.R., Luo L., Sankaranarayanan N.V., Nagarajan B., Vivès R.R., Baleux F., Desai U.R., Arenzana-Seidedos F. and Lortat-Jacob H. Solution structure of CXCL13 and heparan sulphate binding show that GAG binding site and biological activity rely on distinct domains.
Open Biology 7, 170133 (2017)

• Connell B.J., Sadir R., Baleux F., Laguri C., Kleman J-P., Luo L., Arenzana-Seisdedos F. and Lortat-Jacob H. Heparan Sulfate differently regulates CXCL12α and CXCL12γ mediated chemotaxis through differential presentation to CXCR4.
Science Signaling 9, ra107 (2016)

• Arien K.K., Baleux F., Desjardins D., Porrot F., Coic Y.-M., Michiels J., Bouchemal K., Bonnaffé D., Bruel T., Schwartz O., Le Grand R., Vanham G., Dereuddre-Bosquet N. and Lortat-Jacob H. CD4-mimetic sulfopeptide conjugates display sub-nanomolar anti-HIV-1 activity and protect macaques against a SHIV162P3 vaginal challenge.
Scientific Reports 6, 34829 (2016)

• Monneau Y., Arenzana-Seisdedos F. and Lortat-Jacob H. The sweet spot : how GAGs help chemokines guide migrating cells.
Journal of leukocyte Biology 99, 935-953 (2016)

• Préchoux A., Halimi C., Simorre J.P., Lortat-Jacob H. and Laguri C. C5-epimerase and 2-O-sulfotransferase associate in vitro to generate contiguous epimerized and 2-O-sulfated heparan sulfate domains.
ACS ChemBiol 10, 1064-1071 (2015)

• Dalonneau F., Liu X.Q., Sadir R., Almodovar J., Mertani H.C., Bruckert F., Albiges-Rizo C., Weidenhaupt M., Lortat-Jacob H. and Picart C. The effect of delivering the chemokine SDF-1α in a matrix-bound manner on myogenesis.
Biomaterials 35, 4525-4535 (2014)

• Saesen E., Sarrazin S., Laguri C., Sadir R., Maurin D., Thomas A., Imberty A. and Lortat-Jacob H. Insights into the mechanism by which Interferon-gamma basic amino acid clusters mediate protein binding to heparan sulfate. J. Am. Chem. Soc. 135, 9384−9390 (2013)

• Sarris M., Masson J.B., Maurin D., Van der Aa L.M., Boudinot P., Lortat-Jacob H. and Herbomel P. Chemokines guide neutrophil interstitial migration by imposing a haptotactic biased random walk.
Current Biol. 22, 2375-2382 (2012)

• Hou Y., Genua M., Tada Batista D., Calemczuk R., Buhot A., Fornarelli P., Koubachi J., Bonnaffé D., Saesen E., Laguri C., Lortat-Jacob H. and Livache T. Continuous Evolution Profiles for Electronic Tongue Based Analysis.
Angew Chem Int Ed Engl. 51 (41), 10394-10398 (2012)

• Lortat-Jacob H., Burhan I., Scarpellini A., Thomas A., Imberty A., Vivès RR., Johnson T., Gutierrez A., and Verderio E.A.M. Transglutaminase-2 interaction with heparin : Identification of a heparin binding site that regulates cell adhesion to fibronectin-transglutaminase-2 matrix. J. Biol. Chem. 287, 18005-18017 (2012)

• Connell B.J., Baleux F., Coic YM., Clayette P., Bonnaffé D and Lortat-Jacob H. A synthetic heparan sulfate-mimetic peptide conjugated to a mini CD4 displays very high anti-HIV-1 activity independently of coreceptor usage.
Chemistry & Biology 19, 131-139 (2012)

• Laguri C., Sapay N., Simorre J.P., Brutscher B. Imberty A., Gans P. and Lortat-Jacob H. 13C-labeled heparan sulfate analogue as a tool to study protein/heparan sulfate interaction by NMR spectroscopy. Application to the CXCL12α chemokine.
J. Am. Chem. Soc. 133, 9642-9645 (2011)

• Boldajipour B., Doitsidou M., Tarbashevich K., Laguri C., Yu S.R., Ries J., Dumstrei K., Thelen S., Dörries J., Messerschmidt E-M., Thelen M., Schwille P., Brand M., Lortat-Jacob H., Raz E. Control of CXCL12 function by ligand subfunctionalization.
Development 138, 2909-2914 (2011)

• Lortat-Jacob H. The molecular basis and functional implications of chemokine interactions with heparan sulphate.
Curr. Opin. Struct. Biol. 19, 543-548 (2009)

• Baleux F., Loureiro-Morais L., Hersant Y., Clayette P., Arenzana-Seisdedos F., Bonnaffé B. Lortat-Jacob H. A synthetic CD4-HS glycoconjugate inhibits both CCR5 and CXCR4 HIV-1 attachment and entry.
Nat. Chem. Biol. 5, 743-748 (2009)

Scientific collaborations

• Dr. D. Bonnaffé, ICMMO, Orsay
• Dr. Y. Bourne, AFMB, Marseille
• Dr. R. Daniel, LAMBE, Université d’Evry-Val d’Essonne
• Dr. B. Huard, IAB, Grenoble
• Dr. J.M. Dura IGH Montpellier
• Dr. J.C.F. Kwok, University of Leeds, UK
• Dr. T. Blankenstein, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany
• Dr. C. Kenyon, Stellenbosch University, Cape Town, South Africa
• Dr. R. Richter, University of Leeds, UK
• Dr. S.C. Hung, Genomics Research Center, Academia Sinica, Taipei, Taiwan