# Structure insight into FtsZ function maintaining under acid stress of Streptococcus mutans

## TL;DR

This study explores how a protein called FtsZ in Streptococcus mutans helps the bacteria survive in acidic conditions, which is important for causing tooth decay.

## Contribution

The study reveals a unique lateral interface in FtsZ and identifies Arg68 as critical for its function under acid stress.

## Key findings

- The crystal structure of SmFtsZ reveals a unique lateral interface.
- Mutation of Arg68 reduces FtsZ activity and acid resistance in S. mutans.
- Arg68 mutation disrupts conformational changes needed for FtsZ function in acidic environments.

## Abstract

Understanding the acid resistance mechanism of S. mutans is crucial for preventing dental caries. FtsZ is the core protein for cell division in bacteria that can polymerize into Z-rings and drive cytokinesis. Our previous study revealed that the FtsZ in S. mutans (SmFtsZ) has higher self-assembly and GTPase activity under acidic stress, which may be responsible for acid resistance and cariogenesis of S. mutans. However, the functional structure mechanism of SmFtsZ under low pH conditions is still unclear. Here, we further reported the crystal structure of S. mutans FtsZ, revealing a unique lateral interface. Through protein polymerization and GTPase activity assay, we experimentally demonstrated that the mutation of Arg68 on this lateral interface significantly reduced the functional activity of FtsZ in an acidic environment. The phenotype assay and rat caries model further showed that the mutation of Arg68 effectively inhibited the acid resistance of S. mutans and the occurrence and progress of dental caries in vivo. By employing a molecular dynamics simulation analysis, we conclude that the mutation of Arg68 disrupts the conformation change necessary for SmFtsZ polymerization under acidic conditions. Our study proposes a novel mechanism to maintain FtsZ function in bacteria and could be a potential target for antimicrobial drugs to inhibit the growth of S. mutans in acidic environments.