The cytoplasmic protein YedX is a potent inhibitor of CsgA amyloid assembly in E. coli

TL;DR

The study reveals that the E. coli protein YedX prevents harmful protein clumping, supporting cell health during amyloid formation.

Contribution

The novel contribution is identifying YedX as an inhibitor of CsgA amyloid assembly in the cytoplasm of E. coli.

Findings

YedX prevents in vitro amyloid assembly of CsgA, maintaining its soluble state.

YedX shares functional similarities with CsgC in preventing protein aggregation.

YedX contributes to protein homeostasis by inhibiting aggregation-prone proteins.

Abstract

Functional amyloids are a class of amyloids that serve important biological functions. One such bacterial functional amyloid is curli, assembled on the cell surface by Escherichia coli during biofilm biogenesis. Curli precursor proteins, CsgA and CsgB, synthesized in the cytoplasm, are highly amyloidogenic. It is imperative to keep the proteins in a soluble, non-aggregated form to prevent intracellular aggregation and cellular toxicity. Chaperones and chaperone-like proteins aid in solubility and proper translocation of curli subunits. Here, we have investigated a new functionality of a cytoplasmic protein, YedX, an E. coli transthyretin-related protein known to function as a hydrolase enzyme in purine metabolism. We established structure-influenced functional parallelism between YedX and CsgC, a chaperone-like protein that prevents immature aggregation of CsgA and CsgB in the periplasmic space. Our biophysical and biochemical studies suggest that YedX alleviates the in vitro amyloid assembly of CsgA, maintaining its native, soluble, and non-toxic state. Our findings unravel a novel function of YedX in keeping aggregation-prone proteins in the soluble state to aid protein homeostasis within the cell.

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