Crystal structure of the membrane attack complex assembly inhibitor BGA71 from the Lyme disease agent Borrelia bavariensis.
Crystal structure of the membrane attack complex assembly inhibitor BGA71 from the Lyme disease agent Borrelia bavariensis.
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DOI：
10.1038/s41598-018-29651-9
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发表时间：
2018-07-26
影响因子：
4.6
通讯作者：
Tars K
中科院分区：
文献类型：
--
作者：
Brangulis K;Akopjana I;Petrovskis I;Kazaks A;Kraiczy P;Tars K
Borrelia (B.) bavariensis, B. burgdorferi, B. afzelii, B. garinii, B. spielmanii, and B. mayonii are the causative agents in Lyme disease. Lyme disease spirochetes reside in infected Ixodes ticks and are transferred to mammalian hosts during tick feeding. Once transmitted, spirochetes must overcome the first line of defense of the innate immune system either by binding complement regulators or by terminating the formation of the membrane attack complex (MAC). In B. bavariensis, the proteins BGA66 and BGA71 inhibit complement activation by interacting with the late complement components C7, C8, and C9, as well as with the formed MAC. In this study, we have determined the crystal structure of the potent MAC inhibitor BGA71 at 2.9 Ǻ resolution. The structure revealed a cysteine cross-linked homodimer. Based on the crystal structure of BGA71 and the structure-based sequence alignment with CspA from B. burgdorferi, we have proposed a potential binding site for C7 and C9, both of which are constituents of the formed MAC. Our results shed light on the molecular mechanism of immune evasion developed by the human pathogenic Borrelia species to overcome innate immunity. These results will aid in the understanding of Lyme disease pathogenesis and pave the way for the development of new strategies to prevent Lyme disease.
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DOI：
10.1107/s090744491003982x
发表时间：
2011-04
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Evans PR
通讯作者：
Evans PR
DOI：
10.1107/s1744309113013249
发表时间：
2013-06
期刊：
Acta crystallographica. Section F, Structural biology and crystallization communications
影响因子：
--
作者：
Caesar JJ;Johnson S;Kraiczy P;Lea SM
通讯作者：
Lea SM
DOI：
10.2119/molmed.2010.00149
发表时间：
2011-03
期刊：
Molecular medicine (Cambridge, Mass.)
影响因子：
--
作者：
Ehrnthaller C;Ignatius A;Gebhard F;Huber-Lang M
通讯作者：
Huber-Lang M
影响因子：
--
作者：
Bhattacharya S;Ploplis VA;Castellino FJ
通讯作者：
Castellino FJ
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K