title: Flexible Linker Modulates Glycosaminoglycan Affinity of Decorin Binding Protein A.
abstract: Decorin binding protein A (DBPA) is a glycosaminoglycan (GAG)-binding adhesin found on the surface of the bacterium Borrelia burgdorferi (B. burgdorferi), the causative agent of Lyme disease. DBPA facilitates bacterial adherence to extracellular matrices of human tissues and is crucial during the early stage of the infection process. Interestingly, DBPA from different strains (B31, N40, and PBr) show significant differences in GAG affinities, but the structural basis for the differences is not clear. In this study, we show that GAG affinity of N40 DBPA is modulated in part by flexible segments that control access to the GAG binding site, such that shortening of the linker leads to higher GAG affinity when analyzed using ELISA, gel mobility shift assay, solution NMR, and isothermal titration calorimetry. Our observation that GAG affinity differences among different B. burgdorferi strains can be attributed to a flexible linker domain regulating access to the GAG-binding domain is novel. It also provides a rare example of how neutral amino acids and dynamic segments in GAG binding proteins can have a large influence on GAG affinity and provides insights into why the number of basic amino acids in the GAG-binding site may not be the only factor determining GAG affinity of proteins.
authors.forename: Ashli
authors.initials: A
authors.lastname: Morgan
authors.affiliation: ‡Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, Texas 77555, United States.
authors.forename: Krishna Mohan
authors.initials: KM
authors.lastname: Sepuru
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
authors.affiliation: ‡Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, Texas 77555, United States.
authors.forename: Krishna
authors.initials: K
authors.lastname: Rajarathnam
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D025065:Borrelia burgdorferi / Q000235:genetics / Q000378:metabolism; D004269:DNA, Bacterial / Q000235:genetics; D058575:Decorin / Q000378:metabolism; D014644:Genetic Variation; D006025:Glycosaminoglycans / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity
chemical_list: D018829:Adhesins, Bacterial; C546878:DCN protein, human; D004269:DNA, Bacterial; C112557:DdpB protein, Borrelia burgdorferi; D058575:Decorin; D006025:Glycosaminoglycans; D011994:Recombinant Proteins; D006493:Heparin