CspZ variant-specific interaction with factor H incorporates a metal site to support Lyme borreliae complement evasion.

ABSTRACT: Polymorphic microbial immune evasion proteins dictate the pathogen species- or strain-specific virulence. Metals can impact how microbial proteins confer host-pathogen interactions, but whether this activity can be allelically variable is unclear. Here, we investigate the polymorphic CspZ protein of Lyme disease spirochete bacteria to assess the role of metals in protein-protein interaction. CspZ facilitates evasion of the complement system, the first line of immune defense through binding to the complement regulator factor H (FH). By obtaining a high-resolution cocrystal CspZ-FH structure, we identified a zinc coordinating the binding of FH SCR6-7 domains to a Glu65 on a loop from CspZ of Borrelia burgdorferi B31. However, zinc is dispensable for human FH binding for CspZ orthologs with a

SUBMITTER: Brangulis K 

PROVIDER: S-EPMC11773018 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature