Structural basis for complement evasion by lyme disease pathogen Borrelia burgdorferi
Authors:
- Arnab Bhattacharjee,
- Jesper S. Oeemig,
- Robert Kołodziejczyk,
- Taru Meri,
- Tommi Kajander,
- Markus J. Lehtinen,
- Hideo Iwai,
- T. Sakari Jokiranta,
- Adrian Goldman
Abstract
Borrelia burgdorferi spirochetes that cause Lyme borreliosis survive for a long time in human serum because they successfully evade the complement system, an important arm of innate immunity. The outer surface protein E (OspE) of B. burgdorferi is needed for this because it recruits complement regulator factor H (FH) onto the bacterial surface to evade complement-mediated cell lysis. To understand this process at the molecular level, we used a structural approach. First, we solved the solution structure of OspE by NMR, revealing a fold that has not been seen before in proteins involved in complement regulation. Next, we solved the x-ray structure of the complex between OspE and the FH C-terminal domains 19 and 20 (FH19-20) at 2.83 Å resolution. The structure shows that OspE binds FH19-20 in a way similar to, but not identical with, that used by endothelial cells to bind FH via glycosaminoglycans. The observed interaction of OspE with FH19-20 allows the full function of FH in down-regulation of complement activation on the bacteria. This reveals the molecular basis for how B. burgdorferi evades innate immunity and suggests how OspE could be used as a potential vaccine antigen. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.
- Record ID
- UAMb06d24d23cba481b8aa721f9d262189d
- Author
- Journal series
- Journal of Biological Chemistry, ISSN 0021-9258
- Issue year
- 2013
- Vol
- 288
- Pages
- 18685-18695
- ASJC Classification
- ; ;
- DOI
- DOI:10.1074/jbc.M113.459040 Opening in a new tab
- Language
- (en) English
- Score (nominal)
- 35
- Score source
- journalList
- Score
- Publication indicators
- = 30; : 2013 = 1.218; : 2013 (2 years) = 4.600 - 2013 (5 years) =4.863
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- Uniform Resource Identifier
- https://researchportal.amu.edu.pl/info/article/UAMb06d24d23cba481b8aa721f9d262189d/
- URN
urn:amu-prod:UAMb06d24d23cba481b8aa721f9d262189d
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or PerishOpening in a new tab system.