title: 13C-labeled heparan sulfate analogue as a tool to study protein/heparan sulfate interactions by NMR spectroscopy: application to the CXCL12α chemokine.
abstract: Heparan sulfate (HS), a polysaccharide of the glycosaminoglycan family characterized by a unique level of complexity, has emerged as a key regulator of many fundamental biological processes. Although it has become clear that this class of molecules exert their functions by interacting with proteins, the exact modes of interaction still remain largely unknown. Here we report the engineering of a (13)C-labeled HS-like oligosaccharide with a defined oligosaccharidic sequence that was used to investigate the structural determinants involved in protein/HS recognition by multidimensional NMR spectroscopy. Using the chemokine CXCL12α as a model system, we obtained experimental NMR data on both the oligosaccharide and the chemokine that was used to obtain a structural model of a protein/HS complex. This new approach provides a foundation for further investigations of protein/HS interactions and should find wide application.
authors.affiliation: CEA, Institut de Biologie Structurale Jean-Pierre Ebel, F-38027 Grenoble Cedex 1, France. cedric.laguri@ibs.fr
authors.forename: Cédric
authors.initials: C
authors.lastname: Laguri
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sapay
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Simorre
authors.forename: Bernhard
authors.initials: B
authors.lastname: Brutscher
authors.forename: Anne
authors.initials: A
authors.lastname: Imberty
authors.forename: Pierre
authors.initials: P
authors.lastname: Gans
authors.forename: Hugues
authors.initials: H
authors.lastname: Lortat-Jacob
mesh_terms: D001665:Binding Sites; D002247:Carbon Isotopes; D054377:Chemokine CXCL12 / Q000737:chemistry / Q000378:metabolism; D006497:Heparan Sulfate / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015336:Molecular Probe Techniques; D009844:Oligosaccharides / Q000737:chemistry; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D002247:Carbon Isotopes; D054377:Chemokine CXCL12; D006497:Heparan Sulfate; D009844:Oligosaccharides; D011506:Proteins