Structural characterization of CspZ, a complement regulator factor H and FHL-1 binding protein from Borrelia burgdorferi
Structural characterization of CspZ, a complement regulator factor H and FHL-1 binding protein from Borrelia burgdorferi
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DOI：
10.1111/febs.12808
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发表时间：
2014-06-01
期刊：
影响因子：
5.4
通讯作者：
Tars, Kaspars
中科院分区：
文献类型：
--
作者：
Brangulis, Kalvis;Petrovskis, Ivars;Tars, Kaspars
伯氏疏螺旋体是莱姆病的病原体，存在于自然界两种不同类型的宿主中——硬蜱和各种哺乳动物生物体中。为了引发疾病并在哺乳动物宿主生物体中生存，伯氏疏螺旋体必须能够转移到新宿主、增殖、附着到不同的组织并抵抗免疫反应。为了抵抗宿主的免疫反应，伯氏疏螺旋体产生至少五种不同的外表面蛋白，这些蛋白可以结合补体调节因子 H (CFH) 和/或 H 因子样蛋白 1 (CFHL-1)。先前已经描述了两种独特折叠的补体结合蛋白的晶体结构，它们属于两个不同的基因家族并且在其他细菌中未发现。本研究报告了来自伯氏疏螺旋体的 CFH 和 CFHL-1 结合蛋白 CspZ（也称为 BbCRASP-2 或 BBH06）的晶体结构，该蛋白属于第三个基因家族。该结构揭示了整体折叠与伯氏疏螺旋体或其他细菌中其他补体结合蛋白的已知结构不同；该结构与蛋白质数据库中存储的任何已知蛋白质的折叠不同。 CspZ 蛋白的 N 端部分形成四螺旋束，具有与 FAT 结构域（粘着斑靶向结构域）和纽蛋白/-连环蛋白家族中发现的相关结构域相似的特征。通过将 CspZ 晶体结构的发现与之前的诱变研究相结合，我们确定了 CspZ 上可能存在 CFH 和 CFHL-1 的结合表面。
Borreliaburgdorferi is the causative agent of Lyme disease and is found in two different types of hosts in nature - Ixodes ticks and various mammalian organisms. To initiate disease and survive in mammalian host organisms, B.burgdorferi must be able to transfer to a new host, proliferate, attach to different tissue and resist the immune response. To resist the host's immune response, B.burgdorferi produces at least five different outer surface proteins that can bind complement regulator factor H (CFH) and/or factor H-like protein 1 (CFHL-1). The crystal structures of two uniquely folded complement binding proteins, which belong to two distinct gene families and are not found in other bacteria, have been previously described. The crystal structure of the CFH and CFHL-1 binding protein CspZ (also known as BbCRASP-2 or BBH06) from B.burgdorferi, which belongs to a third gene family, is reported in this study. The structure reveals that the overall fold is different from the known structures of the other complement binding proteins in B.burgdorferi or other bacteria; this structure does not resemble the fold of any known protein deposited in the Protein Data Bank. The N-terminal part of the CspZ protein forms a four-helix bundle and has features similar to the FAT domain (focal adhesion targeting domain) and a related domain found in the vinculin/-catenin family. By combining our findings from the crystal structure of CspZ with previous mutagenesis studies, we have identified a likely binding surface on CspZ for CFH and CFHL-1.