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Structural analysis of the outer surface proteins from Borrelia burgdorferi paralogous gene family 54 that are thought to be the key players in the pathogenesis of Lyme disease.
Journal of Structural Biology ( IF 3 ) Pub Date : 2020-03-02 , DOI: 10.1016/j.jsb.2020.107490
Kalvis Brangulis 1 , Inara Akopjana 1 , Ivars Petrovskis 1 , Andris Kazaks 1 , Kaspars Tars 2
Affiliation  

Lyme disease is a tick-borne infection caused by Borrelia burgdorferi sensu lato complex spirochetes. Through a complex enzootic cycle, the bacteria transfer between two different hosts: Ixodes ticks and mammalian organisms. At the start of the tick blood meal, the spirochetes located in the tick gut upregulate the expression of several genes, mainly coding for outer surface proteins. Outer surface proteins belonging to the paralogous gene family 54 (PFam54) have been shown to be the most upregulated among the other borrelial proteins and the results clearly point to the potential importance of these proteins in the pathogenesis of Lyme disease. The significance of PFam54 proteins is confirmed by the fact that of all ten PFam54 proteins, BBA64 and BBA66 are necessary for the transfer of B. burgdorferi from infected Ixodes ticks to mammalian hosts. To enhance the understanding of the pathogenesis of Lyme disease and to promote the development of novel therapies against Lyme disease, we solved the crystal structure of the PFam54 member BBA65. Additionally, we report the structure of the B. burgdorferi BBA64 orthologous protein from B. spielmanii. Together with the previously determined crystal structures of five PFam54 members and several related proteins, we performed a comprehensive structural analysis for this important group of proteins. In addition to revealing the molecular aspects of the proteins, the structural data analysis suggests that the gene families PFam54 and PFam60, which have long been referred to as separate paralogous families, should be merged into one and designated as PFam54_60.

中文翻译:

伯氏疏螺旋体旁系基因家族54的外表面蛋白的结构分析,被认为是莱姆病发病的关键因素。

莱姆病是由博氏疏螺旋体复合螺旋体引起的a传播感染。通过复杂的生化循环,细菌在两个不同的宿主之间转移:x虱和哺乳动物。在the血粉开始时,位于the肠中的螺旋体会上调几个基因的表达,这些基因主要编码外表面蛋白。已经证明,属于旁系基因家族54(PFam54)的外表面蛋白在其他硼蛋白中被上调程度最高,结果清楚地表明了这些蛋白在莱姆病发病机理中的潜在重要性。事实证明,在所有十种PFam54蛋白中,BBA64和BBA66对于将B. burgdorferi从感染的x虱传到哺乳动物宿主中都是必需的,这一事实证实了PFam54蛋白的重要性。为了增进对莱姆病发病机理的了解并促进针对莱姆病的新疗法的发展,我们解决了PFam54成员BBA65的晶体结构。此外,我们报告了B. spielmanii的B. burgdorferi BBA64直系同源蛋白的结构。连同先前确定的五个PFam54成员和几个相关蛋白质的晶体结构,我们对这一重要蛋白质组进行了全面的结构分析。除了揭示蛋白质的分子方面,结构数据分析还表明,长期以来被称为单独的旁系同源家族的基因家族PFam54和PFam60应该合并为一个,并命名为PFam54_60。
更新日期:2020-03-26
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