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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\n                    <jats:italic>S. mutans<\/jats:italic>\n                    (SmFtsZ) has higher self-assembly and GTPase activity under acidic stress, which may be responsible for acid resistance and cariogenesis of\n                    <jats:italic>S. mutans<\/jats:italic>\n                    . However, the functional structure mechanism of SmFtsZ under low pH conditions is still unclear. Here, we further reported the crystal structure of\n                    <jats:italic>S. mutans<\/jats:italic>\n                    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\n                    <jats:italic>S. mutans<\/jats:italic>\n                    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\n                    <jats:italic>S. mutans<\/jats:italic>\n                    in acidic environments.\n                  <\/jats:p>","DOI":"10.1038\/s41368-025-00400-9","type":"journal-article","created":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T00:02:24Z","timestamp":1767484944000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Structure insight into FtsZ function maintaining under acid stress of Streptococcus mutans"],"prefix":"10.1038","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4618-0971","authenticated-orcid":false,"given":"Yuxing","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongliang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4273-4398","authenticated-orcid":false,"given":"Jiahao","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liuchang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqi","family":"Chi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengjiao","family":"Xin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianyang","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqin","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manas","family":"Mondal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,4]]},"reference":[{"key":"400_CR1","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/S0140-6736(07)60031-2","volume":"369","author":"RH Selwitz","year":"2007","unstructured":"Selwitz, R. 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