Structure of decorin binding protein B from Borrelia burgdorferi and its interactions with glycosaminoglycans

Abstract

Decorin-binding proteins (DBPs), DBPA and DBPB, are surface lipoproteins on Borrelia burgdorferi, causative agent of Lyme disease. DBPs bind to the connective tissue proteoglycan decorin and facilitate tissue colonization by the bacterium. Although structural and biochemical properties of DBPA are well understood, little is known about DBPB. In current work, we determined the solution structure of DBPB from strain B31 of B. burgdorferi and characterized its interactions with glycosaminoglycans (GAGs). Our structure shows DBPB adopts the same topology as DBPA, but possesses a much shorter terminal helix, resulting in a longer unstructured C-terminal tail, which is also rich in basic amino acids. Characterization of DBPB-GAG interactions reveals that, despite similar GAG affinities of DBPA and DBPB, the primary GAGbinding sites in DBPB are different from DBPA. In particular, our results indicate lysines in the Cterminus of DBPB are vital to DBPB's ability to bind GAGs whereas C-terminal tail for DBPA from strain B31 only plays a minor role in facilitating GAG bindings. Furthermore, the traditional GAG-binding pocket important to DBPA-GAG interactions is only secondary to DBPB's GAGbinding ability.

Multifunctional and Redundant Roles of Borrelia burgdorferi Outer Surface Proteins in Tissue Adhesion, Colonization, and Complement Evasion

“…also produce proteins, which have been shown to bind to a variety of GAGs. Just as was seen with BBK32, outer surface proteins DbpA and B, produced during mammalian infection ( 37 ), have been shown to bind to decorin, heparin, dermatan sulfate, and heparan sulfate in vitro ( 66 – 68 , 113 – 115 ). OspF-related family members, ErpG, ErpK, and ErpL, were all found to bind to heparan sulfate, in addition to plasminogen, with varying affinities as determined by a series of in vitro assays ( 97 ).…”

NMR Characterization of the Interactions Between Glycosaminoglycans and Proteins

“…Decorin binding protein B (DBPB) bound to DS in a different binding mode than DBPA, mainly through the linker between helices 1 and 2, the C-terminal tail, and the alkaline patch ( Feng and Wang, 2015 ). In the PRE experiment, there were no clear data indicating that the C-terminal tail was involved in binding.…”

Glycosaminoglycan-Protein Interactions by Nuclear Magnetic Resonance (NMR) Spectroscopy

“…Paramagnetically labeled GAG ligands have proven to be useful in structural studies of GAGs’ interactions with several different proteins [ 31 , 45 , 46 , 47 , 48 , 49 ]. The paramagnetic effect relies on the dipole-dipole interactions between unpaired electrons and surrounding atoms.…”

“…This is ideal for detecting long-range or transient contacts between GAGs and proteins. In several works [ 45 , 46 , 47 ], GAG ligands have been functionalized with the paramagnetic tag TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) through the reductive amination of the reducing end of the oligosaccharide ( Figure 11 ). This method has the distinct advantage of being specific to the reducing end of the GAG ligand, allowing for the location of the reducing end of the ligand to be identified.…”

“…They found that GAG binding does not change the ps-to-ns timescale motion of DBPB. However, dermatan sulfate oligosaccharides were able to induce slow timescale motion of the residues in the GAG-binding site [ 46 ]. Interestingly, this phenomenon is only seen with dermatan sulfate and not other GAGs, such as heparin, indicating that the kinetics of interaction between DBPB and GAG is GAG-type specific.…”