Blocking activation of the C1r zymogen defines a novel mode of complement inhibition.

ABSTRACT: Many hematophagous organisms secrete inhibitors of the coagulation and complement systems as constituents of their salivary fluid. Whereas previous studies on salivary gland extracts from the sandfly Lutzomyia longipalpis identified SALO (salivary anticomplement from L. longipalpis) as a potent inhibitor of the classical complement pathway (CP), its precise mechanism of action has remained elusive. Here, we show that SALO inhibits the CP by binding selectively to the C1r zymogen. Using surface plasmon resonance, we found that SALO expressed by human embryonic kidney 293(T) cells (eSALO-WT) bound with nanomolar affinity to the zymogen of complement protease C1r (pro-C1r), but that it did not bind the enzymatically active form of C1r. To gain insight into the structural basis for CP inhibiti

SUBMITTER: Duan H 

PROVIDER: S-EPMC11928764 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature