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 previou...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 ca riogenesis 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.展开更多
As an important group of plant cellular organelles, the molecular mechanism of plastid division is poorly understood. Recent studies have revealed that the homologs of ftsZ gene, an essential prokaryotic cell division...As an important group of plant cellular organelles, the molecular mechanism of plastid division is poorly understood. Recent studies have revealed that the homologs of ftsZ gene, an essential prokaryotic cell division gene, are involved in plastid division process of plant cells. Antisense and sense expression constructions were employed to investigate the functions of the two ftsZ genes, NtFtsZ1 and NtFtsZ2, in transgenic Nicotiana tabacum L. plants. Although antisense expression of,NtFtsZs reduced the native protein level obviously, the size and number of chloroplasts in transgenic tobacco plants had no effect. In contrast, overexpression of NtFtsZs in transgenic plants strikingly changed the number and morphology of chloroplasts. Even only 1 - 2 huge chloroplasts could be seen in the mesophyll cells of some overexpression transgenic plants. Analyses of chloroplast ultrastructures and chlorophyll content of different transgenic plants suggested that NtFtsZs gene have no direct influence on the normal development and function of chloroplasts. ne changes in chloroplast morphology must be a compensation for the change in chloroplast number. The different phenotypes of chloroplasts in antisense and sense transgenic plants implied that different members from the same ftsZ gene family may have similar function in controlling plastid division. Meanwhile, the changes of chloroplast morphology in sense transgenic plants represented the possible plastoskeleton function of ftsZ in higher plant.展开更多
基金supported by the Beijing Natural Science Foundation:7222220National Natural Science Foundation of China (82001039)+2 种基金Research Foundation of Peking University School and Hospital of Stomatology:PKUSS20230117The Fundamental Research Funds for the Central UniversitiesYoung Elite Scientist Sponsorship Program by CAST (No.2019QNRC001 to Y.L.L)。
文摘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 ca riogenesis 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.
文摘As an important group of plant cellular organelles, the molecular mechanism of plastid division is poorly understood. Recent studies have revealed that the homologs of ftsZ gene, an essential prokaryotic cell division gene, are involved in plastid division process of plant cells. Antisense and sense expression constructions were employed to investigate the functions of the two ftsZ genes, NtFtsZ1 and NtFtsZ2, in transgenic Nicotiana tabacum L. plants. Although antisense expression of,NtFtsZs reduced the native protein level obviously, the size and number of chloroplasts in transgenic tobacco plants had no effect. In contrast, overexpression of NtFtsZs in transgenic plants strikingly changed the number and morphology of chloroplasts. Even only 1 - 2 huge chloroplasts could be seen in the mesophyll cells of some overexpression transgenic plants. Analyses of chloroplast ultrastructures and chlorophyll content of different transgenic plants suggested that NtFtsZs gene have no direct influence on the normal development and function of chloroplasts. ne changes in chloroplast morphology must be a compensation for the change in chloroplast number. The different phenotypes of chloroplasts in antisense and sense transgenic plants implied that different members from the same ftsZ gene family may have similar function in controlling plastid division. Meanwhile, the changes of chloroplast morphology in sense transgenic plants represented the possible plastoskeleton function of ftsZ in higher plant.
