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Institut de Biologie StructuraleGrenoble / France

Contacts relatifs à cet article / LORTAT-JACOB Hugues

Activité Scientifique de l’équipe SAGAG / Lortat-Jacob

Thématique scientifique

L’équipe développe deux axes de recherches qui visent à : (1) analyser les relations structures-fonctions des interactions protéine-glycosaminoglycane, en utilisant principalement des cytokines ou des pathogènes comme modèles d’études et :(2) caractériser les mécanismes déterminant les séquences oligosaccharidiques des motifs fonctionnels des HS en étudiant la machinerie biosynthétique de ces molécules.

Membres de l’équipe

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

Anciens membres
• 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)

Publications principales (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)

Collaborations scientifiques

• 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