Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA.
Biochemistry. 2012 Oct 23;51(42):8353-62. doi: 10.1021/bi3007093. Epub 2012 Oct 8.
Decorin-binding protein A (DBPA) is an important lipoprotein from the bacterium Borrelia burgdorferi, the causative agent of Lyme disease. The absence of DBPA drastically reduces the pathogenic potential of the bacterium, and biochemical evidence indicates DBPA's interactions with the glycosaminoglycan (GAG) portion of decorin are crucial to its function. We have determined the solution structure of DBPA and studied DBPA's interactions with various forms of GAGs. DBPA is determined to be a helical bundle protein consisting of five helices held together by a strong hydrophobic core. The structure also possesses a basic patch formed by portions of two helices and two flexible linkers. Low-molecular mass heparin-induced chemical shift perturbations for residues in the region as well as increases in signal intensities of select residues in their presence confirm residues in the pocket are perturbed by heparin binding. Dermatan sulfate fragments, the dominant GAG type found on decorin, were shown to have lower affinity than heparin but are still capable of binding DBPA.
结合蛋白 A（DBPA）是伯氏疏螺旋体（Borrelia burgdorferi）中的一种重要脂蛋白，伯氏疏螺旋体是莱姆病的病原体。DBPA 的缺失极大地降低了细菌的致病潜能，生化证据表明 DBPA 与核心蛋白聚糖（decorin）糖胺聚糖（GAG）部分的相互作用对其功能至关重要。我们已经确定了 DBPA 的溶液结构，并研究了 DBPA 与各种形式 GAG 的相互作用。DBPA 被确定为一种由五个螺旋组成的螺旋束蛋白，由一个强疏水核心保持在一起。该结构还具有由两个螺旋和两个柔性接头的部分形成的碱性斑点。口袋中残基的低分子量肝素诱导的化学位移扰动以及存在肝素时某些残基信号强度的增加证实了肝素结合会扰乱口袋中残基的构象。在核心蛋白聚糖上发现的主要 GAG 类型硫酸皮肤素片段的亲和力低于肝素，但仍能够与 DBPA 结合。
