A Structural Basis for Inhibition of the Complement Initiator Protease C1r by Lyme Disease Spirochetes.

ABSTRACT: Complement evasion is a hallmark of extracellular microbial pathogens such as Borrelia burgdorferi, the causative agent of Lyme disease. Lyme disease spirochetes express nearly a dozen outer surface lipoproteins that bind complement components and interfere with their native activities. Among these, BBK32 is unique in its selective inhibition of the classical pathway. BBK32 blocks activation of this pathway by selectively binding and inhibiting the C1r serine protease of the first component of complement, C1. To understand the structural basis for BBK32-mediated C1r inhibition, we performed crystallography and size-exclusion chromatography-coupled small angle X-ray scattering experiments, which revealed a molecular model of BBK32-C in complex with activated human C1r. Structure-guid

SUBMITTER: Garrigues RJ 

PROVIDER: S-EPMC8612984 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature