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Publication Abstract from PubMed

Decorin binding protein A (DBPA) is an important surface adhesin of the bacterium Borrelia burgdorferi, the causative agent of Lyme disease. DBPA facilitates the bacteria's colonization of human tissue by adhering to glycosaminoglycan (GAG), a sulfated polysaccharide. Interestingly, DBPA sequence variation among different strains of Borrelia spirochetes is high, resulting in significant differences in their GAG affinities. However, the structural mechanisms contributing to these differences are unknown. We determined the solution structures of DBPAs from strain N40 of Borrelia burgdorferi and strain PBr of Borrelia gariini, two DBPA variants whose GAG affinities deviate significantly from strain B31, the most well studied version of DBPA. Our structures revealed that significant differences exist between PBr DBPA and B31/N40 DBPAs. In particular, the C-terminus of PBr DBPA, unlike C-termini from B31 and N40 DBPAs, is positioned away from the GAG-binding pocket, and the linker between helices one and two of PBr DBPA is highly structured and retracted from the GAG-binding pocket. The repositioning of the C-terminus allowed the formation of an extra GAG-binding epitope in PBr DBPA, and the retracted linker give GAG ligands more access to the GAG-binding epitopes than other DBPAs. Characterization of GAG ligands' interactions with wild type PBr and mutants confirmed the importance of the second major GAG-binding epitope and established the fact that the two epitopes are independent of one another and the new epitope is as important to GAG binding as the traditional epitope.

Structural Mechanisms Underlying Sequence-Dependent Variations in GAG Affinities of Decorin Binding Protein A, a Borrelia burgdorferi Adhesin.,Morgan AM, Wang X Biochem J. 2015 Feb 19. PMID:25695518^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.