Crystal structures of the Erp protein family members ErpP and ErpC from Borrelia burgdorferi reveal the reason for different affinities for complement regulator factor H
Date
2015
Authors
Brangulis, Kalvis
Petrovskis, Ivars
Kazaks, Andris
Akopjana, Inara
Tars, Kaspars
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Abstract
Borrelia burgdorferi is the causative agent of Lyme disease, which can be acquired after the bite of an infected
Ixodes tick. As a strategy to resist the innate immunity and to successfully spread and proliferate, B. burgdorferi
expresses a set of outermembrane proteins that are capable of binding complement regulator factorH(CFH), factor
H-like protein 1 (CFHL-1) and factor H-related proteins (CFHR) to avoid complement-mediated killing.
B. burgdorferi B31 contains three proteins that belong to the Erp (OspE/F-related) protein family and are capable
of binding CFH and some CFHRs, namely ErpA, ErpC and ErpP. We have determined the crystal structure of ErpP
at 2.53 Å resolution and the crystal structure of ErpC at 2.15 Å resolution. Recently, the crystal structure of the Erp
familymember OspE fromB. burgdorferi N40was determined in complexwith CFH domains 19–20, revealing the
residues involved in the complex formation. Despite the high sequence conservation between ErpA, ErpC, ErpP
and the homologous protein OspE (78–80%), the affinity for CFH and CFHRs differsmarkedly among the Erp family
members, suggesting that ErpC may bind only CFHRs but not CFH. A comparison of the binding site in OspE
with those of ErpC and ErpP revealed that the extended loop region,which is only observed in the potential binding
site of ErpC, plays an important role by preventing the binding of CFH. These results can explain the inability
of ErpC to bind CFH, whereas ErpP and ErpA still possess the ability to bind CFH.
Description
Keywords
Lyme borreliosis , Borrelia, Ixodes , Spirochetes , Complement , Lyme disease therapy , Outer surface proteins , Research Subject Categories::NATURAL SCIENCES::Biology