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Title:Biophysical Studies of Pathogen Recognition by C-Type Lectins
Author(s):Menon, Sindhu
Doctoral Committee Chair(s):Leckband, Deborah E.
Department / Program:Chemistry
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Chemistry, Physical
Biophysics, Medical
Biophysics, General
Abstract:C-type lectins are a prominent class of pathogen recognition receptors in the innate immune system. The three pathogen recognition lectins studied in this thesis are the mannose binding protein (MBP), the dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN) and the dendritic cell-specific ICAM-3 grabbing nonintegrin related protein (DC-SIGNR). The lectin architecture comprises of the neck region that presents the carbohydrate recognition domains (CRDs) in a cluster of the C-terminus. The neck consists of identical domains that vary in number resulting in various polymorphic forms. The lectins selectively bind to specific oligosaccharide structures on pathogen surfaces through the CRDs. However, the lectin-carbohydrate interactions are exploited by pathogens to infect host cells. To understand the rules that govern pathogen recognition by lectins in more depth, I first investigated the effect of ligand characteristics, namely, surface density and lateral mobility on the binding properties of MBP, DC-SIGN and DC-SIGNR. Secondly, using the polymorphic forms of DC-SIGNR, I explored the impact of the neck structure on the ligand binding properties of the lectins. I addressed these questions using the surface plasmon resonance and the surface forces apparatus. The results reveal that mutability in ligand density is central to pathogen recognition by lectins. Further, the lateral mobility of the ligand substantially impacts the adhesion strength of C-type lectins, presumably due to the spatial adaptation of the ligands to the spatial arrangement of CRDs on the protein. Finally, the force measurements on the polymorphic forms of DC-SIGNR suggest that ligand binding by lectins strongly depend on its oligomeric organization.
Issue Date:2009
Description:161 p.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2009.
Other Identifier(s):(UMI)AAI3363035
Date Available in IDEALS:2014-12-17
Date Deposited:2009

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