The novel heparin-binding motif in decorin-binding protein A from strain B31 of Borrelia burgdorferi explains the higher binding affinity.
The novel heparin-binding motif in decorin-binding protein A from strain B31 of Borrelia burgdorferi explains the higher binding affinity.
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DOI：
10.1021/bi401376u
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发表时间：
2013-11-19
期刊：
影响因子：
2.9
通讯作者：
Wang, Xu
中科院分区：
文献类型：
--
作者：
Morgan, Ashli;Wang, Xu
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. Due to 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 the 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 Borrelia 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 plays a significant role in determining affinity and orientation of GAG-binding to DBPA is specific. Thermodynamic contributions of the new motif to GAG binding was also characterized with both NMR and ITC and compared with 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 to the previous observed differences in GAG affinities of DBPA variants from different Borrelia strains and increases our understanding of DBPA-GAG interactions.
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