title: The novel heparin-binding motif in decorin-binding protein A from strain B31 of Borrelia burgdorferi explains the higher binding affinity.
abstract: Decorin-binding protein A (DBPA), a glycosaminoglycan (GAG)-binding lipoprotein found in Borrelia burgdorferi, is crucial to the transmission of Lyme disease in its earliest stages. Because of its role in the initial transmission of the disease, DBPA is an ideal target for vaccine development. DBPA sequences from different strains also contain considerable heterogeneity, leading to differing affinities for GAGs and proteoglycans among different DBPA sequences. Through biophysical and structural analysis of DBPA from strain B31, we have discovered a novel and important GAG-binding epitope in B31 DBPA. Removal of the epitope greatly attenuated its affinity for DBPA and may explain the differential GAG affinities seen in DBPAs from other strains of B. burgdorferi. Paramagnetic perturbation of the protein with TEMPO-labeled heparin fragments showed bound GAGs are located close to the linker region containing the BXBB motif that plays a significant role in determining the specific affinity and orientation of binding of GAG to DBPA. Thermodynamic contributions of the new motif to GAG binding were also characterized by both nuclear magnetic resonance and isothermal titration calorimetry and compared with those of other DBPA residues previously known to be involved in GAG interactions. These analyses showed the motif is as important as other known binding epitopes. The discovery of the motif offers a possible structural explanation for the previously observed differences in GAG affinities of DBPA variants from different Borrelia strains and improves our understanding of DBPA-GAG interactions.
authors.affiliation: Department of Chemistry & Biochemistry, Arizona State University , Tempe, Arizona 85287, United States.
authors.forename: Ashli
authors.initials: A
authors.lastname: Morgan
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D025065:Borrelia burgdorferi / Q000276:immunology / Q000378:metabolism; D000939:Epitopes / Q000276:immunology*; D006025:Glycosaminoglycans / Q000378:metabolism; D006493:Heparin / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D008193:Lyme Disease / Q000635:transmission; D013816:Thermodynamics
chemical_list: D018829:Adhesins, Bacterial; C112557:DdpB protein, Borrelia burgdorferi; D000939:Epitopes; D006025:Glycosaminoglycans; D006493:Heparin