title: Kinetic and Structural Studies of Interactions between Glycosaminoglycans and Langerin.
abstract: Langerin, a C-type lectin, is expressed in Langerhans cells. It was reported that langerin binds sulfated glycans, which is an important initial step for its role in blocking human immunodeficiency virus (HIV) transmission by capturing HIV pathogens and mediating their internalization into Birbeck granules for their elimination. It is fundamentally important to understand these interactions at the molecular level for the design of new highly specific therapeutic agents for HIV. Surface plasmon resonance (SPR), which allows for the real-time, direct, quantitative analysis of the label-free molecular interactions, has been used successfully for biophysical characterization of glycosaminoglycan (GAG)-protein interactions. In this study, we report kinetics, structural analysis, and the effects of physiological conditions (e.g., pH, salt concentration, and Ca(2+) and Zn(2+)concentrations) on the interactions between GAGs and langerin using SPR. SPR results revealed that langerin binds to heparin with high affinity (KD ∼ 2.4 nM) and the oligosaccharide length required for the interactions is larger than a tetrasaccharide. This heparin/heparan sulfate-binding protein also interacts with other GAGs, including dermatan sulfate, chondroitin sulfates C-E and KS. In addition, liquid chromatography-mass spectrometry analysis was used to characterize the structure of sulfated glycans that bound to langerin.
authors.affiliation: College of Food Science & Nutritional Engineering, China Agricultural University (CAU) , Beijing 100083, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Xinyue
authors.initials: X
authors.lastname: Liu
authors.forename: Chelsea
authors.initials: C
authors.lastname: Kao
authors.forename: Emily
authors.initials: E
authors.lastname: Zhang
authors.affiliation: College of Food Science & Nutritional Engineering, China Agricultural University (CAU) , Beijing 100083, China.
authors.forename: Quanhong
authors.initials: Q
authors.lastname: Li
authors.forename: Fuming
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Departments of Biology and Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute , Troy, New York 12180, United States.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Linhardt
mesh_terms: D015703:Antigens, CD / Q000737:chemistry* / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D037181:Lectins, C-Type / Q000737:chemistry* / Q000378:metabolism*; D037241:Mannose-Binding Lectins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D015703:Antigens, CD; C121916:CD207 protein, human; D006025:Glycosaminoglycans; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D006493:Heparin