Structural and functional analysis of BB0689 from Borrelia burgdorferi, a member of the bacterial CAP superfamily
Structural and functional analysis of BB0689 from Borrelia burgdorferi, a member of the bacterial CAP superfamily
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DOI：
10.1016/j.jsb.2015.09.007
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发表时间：
2015-12-01
影响因子：
3
通讯作者：
Tars, Kaspars
中科院分区：
文献类型：
--
作者：
Brangulis, Kalvis;Jaudzems, Kristaps;Tars, Kaspars
伯氏疏螺旋体是莱姆病的病原体，在蜱叮咬后由受感染的硬蜱传播给哺乳动物宿主。来自B的外表面蛋白BB 0689。当蜱进食时，burgdorferi上调，这表明BB 0689在莱姆病发病机制中的潜在作用。我们测定了BB0689的晶体结构，表明该蛋白属于CAP超家族。尽管CAP结构域广泛存在于生命的所有三个细胞结构域中，但到目前为止，CAP结构域仅在真核生物中进行了研究，其中它通常与某些其他结构域连接以形成多结构域蛋白，并且与哺乳动物生殖道，植物对病原体的反应，昆虫和爬行动物的毒液过敏原以及人类脑肿瘤的生长有关。虽然分离的CAP结构域的确切功能仍然不明确，但最近已将包括胆固醇、脂质和硫酸乙酰肝素的结合在内的几种功能归因于不同的CAP结构域蛋白。在这项研究中，细菌CAP结构域的结构进行了分析，并与以前解决的代表性CAP的晶体结构进行了比较，并检查了BB0689的功能。为了确定BB 0689的潜在功能并确定归因于CAP结构域蛋白的功能是否保守，分析了先前报道的CAP结构域相互作用配偶体的结合，结果表明BB 0689具有尚待发现的独特功能。(C)2015 Elsevier Inc. All rights reserved.
Spirochete Borrelia burgdorferi is the causative agent of Lyme disease and is transmitted from infected Ixodes ticks to a mammalian host after a tick bite. The outer surface protein BB0689 from B. burgdorferi is up-regulated when the tick feeds, which indicates a potential role for BB0689 in Lyme disease pathogenesis. We have determined the crystal structure of BB0689, which revealed that the protein belongs to the CAP superfamily. Though the CAP domain is widespread in all three cellular domains of life, thus far the CAP domain has been studied only in eukaryotes, in which it is usually linked to certain other domains to form a multi-domain protein and is associated with the mammalian reproductive tract, the plant response to pathogens, venom allergens from insects and reptiles, and the growth of human brain tumors. Though the exact function of the isolated CAP domain remains ambiguous, several functions, including the binding of cholesterol, lipids and heparan sulfate, have been recently attributed to different CAP domain proteins. In this study, the bacterial CAP domain structure was analyzed and compared with the previously solved crystal structures of representative CAPs, and the function of BB0689 was examined. To determine the potential function of BB0689 and ascertain whether the functions that have been attributed to the CAP domain proteins are conserved, the binding of previously reported CAP domain interaction partners was analyzed, and the results suggested that BB0689 has a unique function that is yet to be discovered. (C) 2015 Elsevier Inc. All rights reserved.