# AccA from Neisseria gonorrhoeae provides a new framework for understanding periplasmic copper metallochaperones

## TL;DR

A metallochaperone called AccA helps deliver copper to an enzyme in Neisseria gonorrhoeae, enabling it to survive in low-oxygen environments.

## Contribution

The study reveals that AccA delivers copper against an affinity gradient, offering a new framework for understanding copper delivery in bacteria.

## Key findings

- AccA delivers Cu(i) to AniA, enabling nitrite respiration in Neisseria gonorrhoeae under low oxygen.
- AniA has a much weaker Cu(i) binding affinity compared to AccA, suggesting a thermodynamically favorable delivery mechanism.
- AccA is essential for AniA activation, as AniA cannot compete with periplasmic copper sources.

## Abstract

Many bacteria use copper (Cu) to drive key redox reactions and energy metabolism, and they often rely on metallochaperones to deliver Cu to Cu-dependent enzymes. However, why delivery by metallochaperones is needed, and why Cu cannot transfer directly from cellular pools to the target enzymes, is not well understood. Here, we show that the PCuAC-family metallochaperone AccA from the periplasm of Neisseria gonorrhoeae delivers Cu to the Cu-dependent nitrite reductase AniA, enabling growth and nitrite respiration in O2-limiting conditions. Although purified AccA binds both Cu(i) and Cu(ii) ions, only the Cu(i)-binding site is essential for activating AniA in N. gonorrhoeae cells. Unexpectedly, the Cu(i)-binding affinity of AniA is >50 times weaker than that of AccA, suggesting that Cu delivery occurs against a favourable affinity gradient. We propose that AccA is needed because AniA cannot compete with the periplasmic milieu for binding Cu, providing a new framework to understand why some Cu-dependent enzymes need metallochaperones to deliver Cu.

The AccA metallochaperone from Neisseria gonorrhoeae delivers Cu(i) against a favourable thermodynamic gradient to the Cu-dependent nitrite reductase AniA.