# Structural basis for transcription activation through cooperative recruitment of MntR

## TL;DR

This study reveals how MntR activates gene expression by cooperatively binding to multiple DNA sites in response to manganese levels.

## Contribution

The paper provides the first structural insight into cooperative DNA binding by MntR for transcription activation.

## Key findings

- Four MntR dimers bind to four low-affinity DNA sites across the mneP promoter region.
- Cooperative binding is facilitated by polar and non-polar contacts between MntR dimers.
- Structural and functional data explain how MntR activates manganese efflux gene expression.

## Abstract

The manganese transport regulator (MntR) from B. subtilis is a dual regulatory protein that responds to heightened Mn2+ availability in the cell by both repressing the expression of uptake transporters and activating the expression of efflux proteins. Recent work indicates that, in its role as an activator, MntR binds several sites upstream of the genes encoding Mn2+ exporters, leading to a cooperative response to manganese. Here, we use cryo-EM to explore the molecular basis of gene activation by MntR and report a structure of four MntR dimers bound to four 18-base pair sites across an 84-base pair regulatory region of the mneP promoter. Our structures, along with solution studies including mass photometry and in vivo transcription assays, reveal that MntR dimers employ polar and non-polar contacts to bind cooperatively to an array of low-affinity DNA-binding sites. These results reveal the molecular basis for cooperativity in the activation of manganese efflux.