Kinetic and Structural Studies of Interactions between Glycosaminoglycans and Langerin
- 3 August 2016
- journal article
- research article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 55 (32), 4552-4559
- https://doi.org/10.1021/acs.biochem.6b00555
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.Keywords
Funding Information
- National Heart, Lung, and Blood Institute (HL062244, HL094463)
This publication has 29 references indexed in Scilit:
- Comparative analysis reveals selective recognition of glycans by the dendritic cell receptors DC-SIGN and LangerinProtein Engineering, Design and Selection, 2011
- C-type lectin Langerin is a β-glucan receptor on human Langerhans cells that recognizes opportunistic and pathogenic fungiMolecular Immunology, 2010
- Dual Specificity of Langerin to Sulfated and Mannosylated Glycans via a Single C-type Carbohydrate Recognition DomainJournal of Biological Chemistry, 2010
- The carbohydrate recognition domain of Langerin reveals high structural similarity with the one of DC-SIGN but an additional, calcium-independent sugar-binding siteMolecular Immunology, 2008
- Langerin is a natural barrier to HIV-1 transmission by Langerhans cellsNature Medicine, 2007
- Langerhans cells utilize CD1a and langerin to efficiently present nonpeptide antigens to T cellsJCI Insight, 2004
- Characterization of carbohydrate recognition by langerin, a C-type lectin of Langerhans cellsGlycobiology, 2003
- Langerin, a Novel C-Type Lectin Specific to Langerhans Cells, Is an Endocytic Receptor that Induces the Formation of Birbeck GranulesImmunity, 2000
- The monoclonal antibody DCGM4 recognizes Langerin, a protein specific of Langerhans cells, and is rapidly internalized from the cell surfaceEuropean Journal of Immunology, 1999
- Dendritic cells and the control of immunityNature, 1998