Localized and efficient curli nucleation requires the chaperone-like amyloid assembly protein CsgF.

Elucidation of the early events in amyloidogenesis is key to understanding the pathology of, and developing therapies for, amyloid diseases. Critical informants about these early events are amyloid assembly proteins that facilitate the transition from monomer to amyloid fiber. Curli are a functional amyloid whose in vivo polymerization requires a dedicated nucleator protein, CsgB, and an assembly protein, CsgF. Here we demonstrate that without CsgF, curli subunits are released from the cell into the media and are inefficiently polymerized, resulting in fewer and mislocalized curli fibers. CsgF is secreted to the cell surface, where it mediates the cell-association and protease-resistance of the CsgB nucleator, suggesting that CsgF is required for specific localization and/or chaperoning of CsgB for full nucleator activity. CsgF is thus critical to achieve localized and efficient nucleation of fiber subunits into functional, cell-associated amyloid.