6FL0

Crystal structure of the membrane attack complex assembly inhibitor BGA71 from Lyme disease agent Borreliella bavariensis

6FL0 の概要

• エントリーDOI: 10.2210/pdb6fl0/pdb
• 分子名称: membrane attack complex assembly inhibitor BGA71 (1 entity in total)
• 機能のキーワード: outer surface protein, complement system inhibitor, immune system
• 由来する生物種: Borreliella bavariensis
• タンパク質・核酸の鎖数: 18
• 化学式量合計: 408810.24

構造登録者

Brangulis, K.,Akopjana, I.,Petrovskis, I.,Kazaks, A.,Tars, K. (登録日: 2018-01-25, 公開日: 2018-08-08, 最終更新日: 2024-11-13)

主引用文献

Brangulis, K.,Akopjana, I.,Petrovskis, I.,Kazaks, A.,Kraiczy, P.,Tars, K.
Crystal structure of the membrane attack complex assembly inhibitor BGA71 from the Lyme disease agent Borrelia bavariensis.
Sci Rep, 8:11286-11286, 2018

PubMed Abstract: 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.

PubMed: 30050126
DOI: 10.1038/s41598-018-29651-9

実験手法

X-RAY DIFFRACTION (2.9 Å)