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Glycobiology Advance Access published online on September 16, 2008
Glycobiology, doi:10.1093/glycob/cwn088
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© The Author 2008. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Sulfated oligosaccharides (heparin and fucoidan) binding and dimerization of stromal cell-derived factor-1 (SDF-1/CXCL 12) are coupled as evidenced by affinity CE-MS analysis

Soraya Fermas1,2, Florence Gonnet1,2, Angela Sutton3, Nathalie Charnaux3, Barbara Mulloy4, Yuguo Du5, Françoise Baleux6 and Régis Daniel1,2

1 Université d’Evry-Val-d’Essonne, Laboratoire Analyse et Modélisation pour la Biologie et l’Environnement, F-91025 Evry, France
2 CNRS UMR 8587, Laboratoire Analyse et Modélisation pour la Biologie et l’Environnement, F-91025 Evry, France
3 Université Paris Nord, Laboratoire Biothérapies, Bénéfices & Risques EA 3410, F-93000 Bobigny, France
4 Laboratory for Molecular Structure, NIBSC, Blanche Lane, South Mimms, Herts EN6 3QG, UK
5 Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, PO Box 2871, Beijing 100085, PR China
6 Institut Pasteur, Département de Biologie Structurale et Chimie, F-75724 Paris Cedex 15, France

Address Correspondence to: Régis Daniel, Université d’Evry-Val-d’Essonne, Laboratoire Analyse et Modélisation pour la Biologie et l’Environnement, Bd F. Mitterrand, F-91025 Evry, France. Fax: +33-1-69-47-7655; E-mail: regis.daniel{at}univ-evry.fr

Received on June 27, 2008; accepted on September 10, 2008

Chemokine Stromal Cell-Derived Factor-1 (SDF-1) is a potent chemo-attractant involved in leukocyte trafficking and metastasis. Heparan sulfate on the cell surface binds SDF-1 and may modulate its function as a co-receptor of this chemokine. A major effect of the glycosaminoglycan binding may be on the quaternary structure of SDF-1, which has been controversially reported as a monomer or a dimer. We have investigated the effect of sulfated oligosaccharides on the oligomerization of SDF-1 and of its mutated form SDF-1 (3/6), using affinity capillary electrophoresis (ACE) hyphenated to mass spectrometry (MS). Coupled to MS, ACE allowed the study for the first time of the effect of size-defined oligosaccharides on the quaternary organization of SDF-1 in µM range concentrations, i.e. lower values than the mM values previously reported in NMR, light scattering and ultracentrifugation experiments. Our results showed that in absence of sulfated oligosaccharides SDF-1 is mostly monomeric in solution. However, dimer formation was observed upon interaction with heparin sulfated oligosaccharides despite the mM Kd values for dimerization. SDF-1/oligosaccharide 2/1 complex was detected, indicating that oligosaccharide binding promoted the dimerization of SDF-1. Heparin tetrasaccharide but not disaccharide promoted dimer formation, suggesting that the dimer required to be stabilized by a long enough bound oligosaccharide. SDF-1/oligosaccharide 1/1 complex was only observed with heparin disaccharide and fucoidan pentasaccharide, pointing out the role of specific structural determinants in promoting dimer formation. These results underline the importance of dimerization induced by glycosaminoglycans for chemokine functionality.

Key words: CE-MS / Chemokine / Fucoidan / Heparin / SDF-1


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