Borrelia burgdorferi Binds Fibronectin through a Tandem β-Zipper, a Common Mechanism of Fibronectin Binding in Staphylococci, Streptococci, and Spirochetes

Abstract

BBK32 is a fibronectin-binding protein from the

Fibronectin Binds to and Induces Conformational Change in a Disordered Region of Leptospiral Immunoglobulin-like Protein B

“…The ␤-strand-rich conformation formed by LigBCen2NR after binding NTD observed via far UV CD spectroscopy suggests that the binding of LigBCen2NR to NTD might be also mediated by a ␤-zipper interaction. However, the entropy-driven interaction of LigBCen2NR and NTD is distinct from the enthalpy-driven binding of other bacterial proteins known to bind NTD via the ␤-zipper interaction (Table 1) (23,39,46). In addition, we are unable to identify substantial sequence similarity between LigBCen2NR and BBK32 or other Fn-binding proteins, so additional study is needed to further characterize the binding between LigBCen2NR and NTD.…”

“…Similarly, upon binding to NTD, LigBCen2NR folds into a ␤-strand-rich structure, much like the D123 domain of FnbPA or the N-terminal of BBK32 (21). High resolution structures of the complex between the B3 region of FnbB and the first and the second type I module of Fn (17,18) and the complex between the first or the fifth Fn binding region of FnbpA and the second to the fifth type I module of Fn (23,39,46) all indicate that a two ␤-strand complex, called a ␤-zipper, mediates those interactions. The binding of Sfb and BBK32 to NTD are also accomplished through the ␤-zipper interaction (23, 39, 46).…”

Fibronectin-binding nanoparticles for intracellular targeting addressed by B. burgdorferi BBK32 protein fragments

“…Different BBK32 peptides used in this study have been shown to bind different FN regions. [25][26][27][28] Our results show that only BF130-166 VLPs demonstrated clear, strong FN-binding ability. Moreover, we were able to show that this binding occurs via GBD of FN.…”

“…It could be explained by the manner of binding of this BBK32 region to the N-terminal modules of FN that require an antiparallel orientation of the binding partners with the peptide forming additional β-strands at the edge of the triple-stranded β-sheets of the two FNI modules (i.e., a "tandem-zipper" mechanism). 26 The 153-175 and 160-175 insertions were predicted as α-helice-forming for all four possible chain variants; therefore we could assume the lack of conformational compatibility in FN binding for these VLPs (Figure 1). However, induction of ordered aggregation of soluble FN and inhibition of endothelial cell proliferation similar to that of anastellin were shown for these BBK32 fragments, so there may be further interest in these constructs in the future.…”

“…25 It was shown that the region of BBK32 comprising amino acids 147 -205 binds to the N-terminal FNI and FNIII modules, but residues 120 -147 of BBK32 protein are considered similar to the FN-binding region of SfbI protein from S. pyogenes that had been shown to bind to the GBD of FN. [26][27][28] Here we present the construction of HBc-based chimeric VLPs with FN-binding property by insertion of B. burgdorferi BBK32 fragments into the MIR region of capsid. The evidence of intracellular internalization of these VLPs into nonphagocytic cells through caveolae-mediated endocytosis makes this construct an attractive model in development of HBc-based NPs for medically relevant cellular targeting applications and highlights the 130 -166 aa fragment of B. burgdorferi BBK32 as a novel cellular uptake-promoting peptide.…”